Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by the dysregulation of molecular pathways and activation of the brain's immune system, resulting in the release of pro-inflammatory and oxidative molecules. This chronic inflammation is exacerbated by peripheral leukocyte infiltration into the central nervous system. Medicinal plants, with their historical use in traditional medicine, have emerged as promising candidates to mitigate neuroinflammation and offer a sustainable alternative for addressing neurodegenerative conditions in a green healthcare framework. This review evaluates the effects of medicinal plants on neuroinflammation, emphasizing their mechanisms of action, effective dosages, and clinical implications, based on a systematic search of databases such as PubMed, SCOPUS, and Web of Science. The key findings highlight that plants like Cleistocalyx nervosum var. paniala, Curcuma longa, Cannabis sativa, and Dioscorea nipponica reduce pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), inhibit enzymes (COX-2 and iNOS), and activate antioxidant pathways, particularly Nrf2. NF-κB emerged as the primary pro-inflammatory pathway inhibited across studies. While the anti-inflammatory potential of these plants is significant, the variability in dosages and phytochemical compositions limits clinical translation. Here, we highlight that medicinal plants are effective modulators of neuroinflammation, underscoring their therapeutic potential. Future research should focus on animal models, standardized protocols, and safety assessments, integrating advanced methodologies, such as genetic studies and nanotechnology, to enhance their applicability in neurodegenerative disease management.

Danube Neuroscience Research Laboratory HUN REN SZTE Neuroscience Research Group Hungarian Research Network University of Szeged Tisza Lajos Krt 113 H 6725 Szeged Hungary

Department of Biochemistry and Pharmacology School of Medicine Faculdade de Medicina de Marília Marília 17519 030 São Paulo Brazil

Department of Biochemistry and Pharmacology School of Medicine Universidade de Marília Marília 17525 902 São Paulo Brazil

Department of Chemistry Faculty of Science University of Hradec Kralove 50003 Hradec Kralove Czech Republic

Department of Gerontology School of Gerontology Universidade Federal de São Carlos São Carlos 13565 905 São Paulo Brazil

Faculty of Health and Social Studies Institute of Radiology Toxicology and Civil Protection University of South Bohemia Ceske Budejovice 37005 Ceske Budejovice Czech Republic

Postgraduate Program in Structural and Functional Interactions in Rehabilitation School of Medicine Universidade de Marília Marília 17525 902 São Paulo Brazil

Zobrazit více v PubMed

Davinelli S., Maes M., Corbi G., Zarrelli A., Willcox D.C., Scapagnini G. Dietary phytochemicals and neuro-inflammaging: From mechanistic insights to translational challenges. Immun. Ageing. 2016;13:16. doi: 10.1186/s12979-016-0070-3. PubMed DOI PMC

Pan T., Xiao Q., Fan H.J., Xu L., Qin S.C., Yang L.X., Jin X.M., Xiao B.G., Zhang B., Ma C.G., et al. Wuzi Yanzong Pill relieves MPTP-induced motor dysfunction and neuron loss by inhibiting NLRP3 inflammasome-mediated neuroinflammation. Metab. Brain Dis. 2023;38:2211–2222. doi: 10.1007/s11011-023-01266-8. PubMed DOI

Tanaka M., Vécsei L. A Decade of Dedication: Pioneering Perspectives on Neurological Diseases and Mental Illnesses. Biomedicines. 2024;12:1083. doi: 10.3390/biomedicines12051083. PubMed DOI PMC

Tanaka M., Vécsei L. Revolutionizing our understanding of Parkinson’s disease: Dr. Heinz Reichmann’s pioneering research and future research direction. J. Neural Transm. 2024;131:1367–1387. doi: 10.1007/s00702-024-02812-z. PubMed DOI PMC

Rink C., Khanna S. Significance of brain tissue oxygenation and the arachidonic acid cascade in stroke. Antioxid. Redox Signal. 2011;14:1889–1903. doi: 10.1089/ars.2010.3474. PubMed DOI PMC

Morozumi T., Preziosa P., Meani A., Albergoni M., Margoni M., Pagani E., Filippi M., Rocca M.A. Influence of cardiorespiratory fitness and MRI measures of neuroinflammation on hippocampal volume in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry. 2024;95:29–36. doi: 10.1136/jnnp-2023-331482. PubMed DOI

Abadin X., de Dios C., Zubillaga M., Ivars E., Puigròs M., Marí M., Morales A., Vizuete M., Vitorica J., Trullas R., et al. Neuroinflammation in Age-Related Neurodegenerative Diseases: Role of Mitochondrial Oxidative Stress. Antioxidants. 2024;13:1440. doi: 10.3390/antiox13121440. PubMed DOI PMC

Solleiro-Villavicencio H., Rivas-Arancibia S. Effect of Chronic Oxidative Stress on Neuroinflammatory Response Mediated by CD4(+)T Cells in Neurodegenerative Diseases. Front. Cell. Neurosci. 2018;12:114. doi: 10.3389/fncel.2018.00114. PubMed DOI PMC

Direito R., Barbalho S.M., Figueira M.E., Minniti G., de Carvalho G.M., de Oliveira Zanuso B., de Oliveira Dos Santos A.R., de Góes Corrêa N., Rodrigues V.D., de Alvares Goulart R., et al. Medicinal Plants, Phytochemicals and Regulation of the NLRP3 Inflammasome in Inflammatory Bowel Diseases: A Comprehensive Review. Metabolites. 2023;13:728. doi: 10.3390/metabo13060728. PubMed DOI PMC

Teleanu D.M., Niculescu A.G., Lungu I.I., Radu C.I., Vladâcenco O., Roza E., Costăchescu B., Grumezescu A.M., Teleanu R.I. An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases. Int. J. Mol. Sci. 2022;23:5938. doi: 10.3390/ijms23115938. PubMed DOI PMC

de Lima E.P., Moretti R.C., Jr., Torres Pomini K., Laurindo L.F., Sloan K.P., Sloan L.A., Castro M.V.M., Baldi E., Jr., Ferraz B.F.R., de Souza Bastos Mazuqueli Pereira E., et al. Glycolipid Metabolic Disorders, Metainflammation, Oxidative Stress, and Cardiovascular Diseases: Unraveling Pathways. Biology. 2024;13:519. doi: 10.3390/biology13070519. PubMed DOI PMC

Girotto O.S., Furlan O.O., Moretti Junior R.C., Goulart R.A., Baldi Junior E., Barbalho-Lamas C., Fornari Laurindo L., Barbalho S.M. Effects of apples (Malus domestica) and their derivatives on metabolic conditions related to inflammation and oxidative stress and an overview of by-products use in food processing. Crit. Rev. Food Sci. Nutr. 2024:1–32. doi: 10.1080/10408398.2024.2372690. PubMed DOI

Valotto Neto L.J., Reverete de Araujo M., Moretti Junior R.C., Mendes Machado N., Joshi R.K., Dos Santos Buglio D., Barbalho Lamas C., Direito R., Fornari Laurindo L., Tanaka M., et al. Investigating the Neuroprotective and Cognitive-Enhancing Effects of Bacopa monnieri: A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis. Antioxidants. 2024;13:393. doi: 10.3390/antiox13040393. PubMed DOI PMC

Silveira Rossi J.L., Barbalho S.M., Reverete de Araujo R., Bechara M.D., Sloan K.P., Sloan L.A. Metabolic syndrome and cardiovascular diseases: Going beyond traditional risk factors. Diabetes/Metab. Res. Rev. 2022;38:e3502. doi: 10.1002/dmrr.3502. PubMed DOI

Tanaka M., Szabó Á., Vécsei L. Redefining Roles: A Paradigm Shift in Tryptophan-Kynurenine Metabolism for Innovative Clinical Applications. Int. J. Mol. Sci. 2024;25:12767. doi: 10.3390/ijms252312767. PubMed DOI PMC

de Lima E.P., Tanaka M., Lamas C.B., Quesada K., Detregiachi C.R.P., Araújo A.C., Guiguer E.L., Catharin V., de Castro M.V.M., Junior E.B., et al. Vascular Impairment, Muscle Atrophy, and Cognitive Decline: Critical Age-Related Conditions. Biomedicines. 2024;12:2096. doi: 10.3390/biomedicines12092096. PubMed DOI PMC

Simpson D.S.A., Oliver P.L. ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease. Antioxidants. 2020;9:743. doi: 10.3390/antiox9080743. PubMed DOI PMC

Fabisiak T., Patel M. Crosstalk between neuroinflammation and oxidative stress in epilepsy. Front. Cell Dev. Biol. 2022;10:976953. doi: 10.3389/fcell.2022.976953. PubMed DOI PMC

Rodriguez-Lopez A., Torres-Paniagua A.M., Acero G., Díaz G., Gevorkian G. Increased TSPO expression, pyroglutamate-modified amyloid beta (AβN3(pE)) accumulation and transient clustering of microglia in the thalamus of Tg-SwDI mice. J. Neuroimmunol. 2023;382:578150. doi: 10.1016/j.jneuroim.2023.578150. PubMed DOI

Laurindo L.F., de Carvalho G.M., de Oliveira Zanuso B., Figueira M.E., Direito R., de Alvares Goulart R., Buglio D.S., Barbalho S.M. Curcumin-Based Nanomedicines in the Treatment of Inflammatory and Immunomodulated Diseases: An Evidence-Based Comprehensive Review. Pharmaceutics. 2023;15:229. doi: 10.3390/pharmaceutics15010229. PubMed DOI PMC

Tanaka M., Battaglia S., Giménez-Llort L., Chen C., Hepsomali P., Avenanti A., Vécsei L. Innovation at the Intersection: Emerging Translational Research in Neurology and Psychiatry. Cells. 2024;13:790. doi: 10.3390/cells13100790. PubMed DOI PMC

Tanaka M., Chen C. Editorial: Towards a mechanistic understanding of depression, anxiety, and their comorbidity: Perspectives from cognitive neuroscience. Front. Behav. Neurosci. 2023;17:1268156. doi: 10.3389/fnbeh.2023.1268156. PubMed DOI PMC

Fornari Laurindo L., Aparecido Dias J., Cressoni Araújo A., Torres Pomini K., Machado Galhardi C., Rucco Penteado Detregiachi C., Santos de Argollo Haber L., Donizeti Roque D., Dib Bechara M., Vialogo Marques de Castro M., et al. Immunological dimensions of neuroinflammation and microglial activation: Exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression. Front. Immunol. 2023;14:1305933. doi: 10.3389/fimmu.2023.1305933. PubMed DOI PMC

Yu M., Wang F., Han K. Silencing of SH3BP2 Inhibits Microglia Activation Via the JAK/STAT Signaling in Spinal Cord Injury Models. Inflammation. 2024 doi: 10.1007/s10753-024-02186-0. PubMed DOI

Cokdinleyen M., Dos Santos L.C., de Andrade C.J., Kara H., Colás-Ruiz N.R., Ibañez E., Cifuentes A. A Narrative Review on the Neuroprotective Potential of Brown Macroalgae in Alzheimer’s Disease. Nutrients. 2024;16:4394. doi: 10.3390/nu16244394. PubMed DOI PMC

Battaglia S., Avenanti A., Vécsei L., Tanaka M. Neurodegeneration in Cognitive Impairment and Mood Disorders for Experimental, Clinical and Translational Neuropsychiatry. Biomedicines. 2024;12:574. doi: 10.3390/biomedicines12030574. PubMed DOI PMC

Hopper A.T., Campbell B.M., Kao H., Pintchovski S.A., Staal R.G.W. Chapter Four—Recent Developments in Targeting Neuroinflammation in Disease. In: Desai M.C., editor. Annual Reports in Medicinal Chemistry. Volume 47. Academic Press; Cambridge, MA, USA: 2012. pp. 37–53.

Liu Y., Yang H., Luo N., Fu Y., Qiu F., Pan Z., Li X., Jian W., Yang X., Xue Q., et al. An Fgr kinase inhibitor attenuates sepsis-associated encephalopathy by ameliorating mitochondrial dysfunction, oxidative stress, and neuroinflammation via the SIRT1/PGC-1α signaling pathway. J. Transl. Med. 2023;21:486. doi: 10.1186/s12967-023-04345-7. PubMed DOI PMC

Bássoli R., Audi D., Ramalho B., Audi M., Quesada K., Barbalho S.M. The Effects of Curcumin on Neurodegenerative Diseases: A Systematic Review. J. Herb. Med. 2023;42:100771. doi: 10.1016/j.hermed.2023.100771. DOI

Barbalho S.M., Direito R., Laurindo L.F., Marton L.T., Guiguer E.L., Goulart R.d.A., Tofano R.J., Carvalho A.C., Flato U.A.P., Capelluppi Tofano V.A., et al. Ginkgo biloba in the aging process: A narrative review. Antioxidants. 2022;11:525. doi: 10.3390/antiox11030525. PubMed DOI PMC

de Oliveira Zanuso B., Dos Santos A.R.d.O., Miola V.F.B., Campos L.M.G., Spilla C.S.G., Barbalho S.M. Panax ginseng and aging related disorders: A systematic review. Exp. Gerontol. 2022;161:111731. doi: 10.1016/j.exger.2022.111731. PubMed DOI

Rangaraju S., Dammer E.B., Raza S.A., Rathakrishnan P., Xiao H., Gao T., Duong D.M., Pennington M.W., Lah J.J., Seyfried N.T., et al. Identification and therapeutic modulation of a pro-inflammatory subset of disease-associated-microglia in Alzheimer’s disease. Mol. Neurodegener. 2018;13:24. doi: 10.1186/s13024-018-0254-8. PubMed DOI PMC

Blank-Stein N., Mass E. Macrophage and monocyte subsets in response to ischemic stroke. Eur. J. Immunol. 2023;53:e2250233. doi: 10.1002/eji.202250233. PubMed DOI

Cotoia A., Charitos I.A., Corriero A., Tamburrano S., Cinnella G. The Role of Macronutrients and Gut Microbiota in Neuroinflammation Post-Traumatic Brain Injury: A Narrative Review. Nutrients. 2024;16:4359. doi: 10.3390/nu16244359. PubMed DOI PMC

Sarsaiya S., Jain A., Shu F., Jia Q., Gong Q., Wu Q., Shi J., Chen J. Unveiling the potential of dendrobine: Insights into bioproduction, bioactivities, safety, circular economy, and future prospects. Crit. Rev. Biotechnol. 2025:1–19. doi: 10.1080/07388551.2024.2438161. PubMed DOI

Yuan H., Ma Q., Ye L., Piao G. The Traditional Medicine and Modern Medicine from Natural Products. Molecules. 2016;21:559. doi: 10.3390/molecules21050559. PubMed DOI PMC

Panche A.N., Diwan A.D., Chandra S.R. Flavonoids: An overview. J. Nutr. Sci. 2016;5:e47. doi: 10.1017/jns.2016.41. PubMed DOI PMC

Menezes A.A., Shah Z.A. A Review of the Consequences of Gut Microbiota in Neurodegenerative Disorders and Aging. Brain Sci. 2024;14:1224. doi: 10.3390/brainsci14121224. PubMed DOI PMC

Park K. The Role of Dietary Phytochemicals: Evidence from Epidemiological Studies. Nutrients. 2023;15:1371. doi: 10.3390/nu15061371. PubMed DOI PMC

Buglio D.S., Marton L.T., Laurindo L.F., Guiguer E.L., Araújo A.C., Buchaim R.L., Goulart R.A., Rubira C.J., Barbalho S.M. The Role of Resveratrol in Mild Cognitive Impairment and Alzheimer’s Disease: A Systematic Review. J. Med. Food. 2022;25:797–806. doi: 10.1089/jmf.2021.0084. PubMed DOI

Barbalho S.M., Bueno Ottoboni A.M.M., Fiorini A.M.R., Guiguer E.L., Nicolau C.C.T., Goulart R.d.A., Flato U.A.P. Grape juice or wine: Which is the best option? Crit. Rev. Food Sci. Nutr. 2020;60:3876–3889. doi: 10.1080/10408398.2019.1710692. PubMed DOI

Laurindo L.F., Direito R., Bueno Otoboni A.M., Goulart R.A., Quesada K., Barbalho S.M. Grape processing waste: Effects on inflammatory bowel disease and colorectal cancer. Food Rev. Int. 2024;40:336–369. doi: 10.1080/87559129.2023.2168281. DOI

Sen T., Samanta S.K. Medicinal plants, human health and biodiversity: A broad review. Adv. Biochem. Eng. Biotechnol. 2015;147:59–110. doi: 10.1007/10_2014_273. PubMed DOI

Shen L., Tian Q., Ran Q., Gan Q., Hu Y., Du D., Qin Z., Duan X., Zhu X., Huang W. Z-Ligustilide: A Potential Therapeutic Agent for Atherosclerosis Complicating Cerebrovascular Disease. Biomolecules. 2024;14:1623. doi: 10.3390/biom14121623. PubMed DOI PMC

Montazeri-Khosh Z., Ebrahimpour A., Keshavarz M., Sheybani-Arani M., Samiei A. Combination therapies and other therapeutic approaches targeting the NLRP3 inflammasome and neuroinflammatory pathways: A promising approach for traumatic brain injury. Immunopharmacol. Immunotoxicol. 2025:1–17. doi: 10.1080/08923973.2024.2444956. PubMed DOI

Pagotto G.L.O., Santos L., Osman N., Lamas C.B., Laurindo L.F., Pomini K.T., Guissoni L.M., Lima E.P., Goulart R.A., Catharin V., et al. Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer’s Dementia: Clinical Trial Systematic Review. Antioxidants. 2024;13:651. doi: 10.3390/antiox13060651. PubMed DOI PMC

Chaachouay N., Zidane L. Plant-Derived Natural Products: A Source for Drug Discovery and Development. Drugs Drug Candidates. 2024;3:184–207. doi: 10.3390/ddc3010011. DOI

Abou Assale T., Afrang N., Wissfeld J., Cuevas-Rios G., Klaus C., Linnartz-Gerlach B., Neumann H. Neuroprotective role of sialic-acid-binding immunoglobulin-like lectin-11 in humanized transgenic mice. Front. Neurosci. 2024;18:1504765. doi: 10.3389/fnins.2024.1504765. PubMed DOI PMC

Kim Y., Lim J., Oh J. Taming neuroinflammation in Alzheimer’s disease: The protective role of phytochemicals through the gut-brain axis. Biomed. Pharmacother. 2024;178:117277. doi: 10.1016/j.biopha.2024.117277. PubMed DOI

Kisioglu B., Onal E., Karabulut D., Onbasilar I., Akyol A. Neuroprotective Roles of Lauric Acid and Resveratrol: Shared Benefits in Neuroinflammation and Anxiety, Distinct Effects on Memory Enhancement. Food Sci. Nutr. 2024;12:9735–9748. doi: 10.1002/fsn3.4520. PubMed DOI PMC

Liu J., Wang Y., Sun H., Lei D., Liu J., Fei Y., Wang C., Han C. Resveratrol ameliorates postoperative cognitive dysfunction in aged mice by regulating microglial polarization through CX3CL1/CX3CR1 signaling axis. Neurosci. Lett. 2024;847:138089. doi: 10.1016/j.neulet.2024.138089. PubMed DOI

Tao G., Wang X., Wang J., Ye Y., Zhang M., Lang Y., Ding S. Dihydro-resveratrol ameliorates NLRP3 inflammasome-mediated neuroinflammation via Bnip3-dependent mitophagy in Alzheimer’s disease. Br. J. Pharmacol. 2024;182:1005–1024. doi: 10.1111/bph.17373. PubMed DOI

Hou B.L., Wang C.C., Liang Y., Jiang M., Sun Y.E., Huang Y.L., Ma Z.L. Analgesic Effect of Dehydrocorydaline on Chronic Constriction Injury-Induced Neuropathic Pain via Alleviating Neuroinflammation. Chin. J. Integr. Med. 2025 doi: 10.1007/s11655-024-3920-4. PubMed DOI

Carles A., Freyssin A., Guehairia S., Reguero T., Vignes M., Hirbec H., Rubinstenn G., Maurice T. Neuroprotection by chronic administration of Fluoroethylnormemantine (FENM) in mouse models of Alzheimer’s disease. Alzheimer’s Res. Ther. 2025;17:7. doi: 10.1186/s13195-024-01648-9. PubMed DOI PMC

Battaglia S., Avenanti A., Vécsei L., Tanaka M. Neural Correlates and Molecular Mechanisms of Memory and Learning. Int. J. Mol. Sci. 2024;25:2724. doi: 10.3390/ijms25052724. PubMed DOI PMC

Tyler S.E.B., Tyler L.D.K. Pathways to healing: Plants with therapeutic potential for neurodegenerative diseases. IBRO Neurosci. Rep. 2023;14:210–234. doi: 10.1016/j.ibneur.2023.01.006. PubMed DOI PMC

Suk K. Regulation of neuroinflammation by herbal medicine and its implications for neurodegenerative diseases. A focus on traditional medicines and flavonoids. Neurosignals. 2005;14:23–33. doi: 10.1159/000085383. PubMed DOI

Janpaijit S., Sillapachaiyaporn C., Theerasri A., Charoenkiatkul S., Sukprasansap M., Tencomnao T. Cleistocalyx nervosum var. paniala Berry Seed Protects against TNF-α-Stimulated Neuroinflammation by Inducing HO-1 and Suppressing NF-κB Mechanism in BV-2 Microglial Cells. Molecules. 2023;28:3057. doi: 10.3390/molecules28073057. PubMed DOI PMC

Janpaijit S., Lertpatipanpong P., Sillapachaiyaporn C., Baek S.J., Charoenkiatkul S., Tencomnao T., Sukprasansap M. Anti-neuroinflammatory effects of Cleistocalyx nervosum var. paniala berry-seed extract in BV-2 microglial cells via inhibition of MAPKs/NF-κB signaling pathway. Heliyon. 2022;8:e11869. doi: 10.1016/j.heliyon.2022.e11869. PubMed DOI PMC

Kim K.W., Lee Y.S., Yoon D., Kim G.S., Lee D.Y. The ethanolic extract of Curcuma longa grown in Korea exhibits anti-neuroinflammatory effects by activating of nuclear transcription factor erythroid-2-related factor 2/heme oxygenase-1 signaling pathway. BMC Complement. Med. Ther. 2022;22:343. doi: 10.1186/s12906-022-03825-5. PubMed DOI PMC

Eun C.S., Lim J.S., Lee J., Lee S.P., Yang S.A. The protective effect of fermented Curcuma longa L. on memory dysfunction in oxidative stress-induced C6 gliomal cells, proinflammatory-activated BV2 microglial cells, and scopolamine-induced amnesia model in mice. BMC Complement. Altern. Med. 2017;17:367. doi: 10.1186/s12906-017-1880-3. PubMed DOI PMC

Borgonetti V., Benatti C., Governa P., Isoldi G., Pellati F., Alboni S., Tascedda F., Montopoli M., Galeotti N., Manetti F., et al. Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids-, and NF-κB-mediated signaling. Phytother. Res. 2022;36:2246–2263. doi: 10.1002/ptr.7458. PubMed DOI PMC

Barbalace M.C., Freschi M., Rinaldi I., Mazzara E., Maraldi T., Malaguti M., Prata C., Maggi F., Petrelli R., Hrelia S., et al. Identification of Anti-Neuroinflammatory Bioactive Compounds in Essential Oils and Aqueous Distillation Residues Obtained from Commercial Varieties of Cannabis sativa L. Int. J. Mol. Sci. 2023;24:16601. doi: 10.3390/ijms242316601. PubMed DOI PMC

Jiang Y.K., Li M.M., Wang S.Y., Hao Z.C., Meng X., Kuang H.X., Yang B.Y., Liu Y. Protective effect of phenylpropionamides in the seed of Cannabis sativa L. on Parkinson’s disease through autophagy. Fitoterapia. 2024;175:105883. doi: 10.1016/j.fitote.2024.105883. PubMed DOI

Borgonetti V., Anceschi L., Brighenti V., Corsi L., Governa P., Manetti F., Pellati F., Galeotti N. Cannabidiol-rich non-psychotropic Cannabis sativa L. oils attenuate peripheral neuropathy symptoms by regulation of CB2-mediated microglial neuroinflammation. Phytother. Res. 2023;37:1924–1937. doi: 10.1002/ptr.7710. PubMed DOI

Zhou Y., Wang S., Ji J., Lou H., Fan P. Hemp (Cannabis sativa L.) Seed Phenylpropionamides Composition and Effects on Memory Dysfunction and Biomarkers of Neuroinflammation Induced by Lipopolysaccharide in Mice. ACS Omega. 2018;3:15988–15995. doi: 10.1021/acsomega.8b02250. PubMed DOI PMC

Shin J., Kim D.U., Bae G.S., Han J.Y., Lim D.W., Lee Y.M., Kim E., Kwon E., Han D., Kim S. Antidepressant-like Effects of Cannabis sativa L. Extract in an Lipopolysaccharide Model: Modulation of Mast Cell Activation in Deep Cervical Lymph Nodes and Dura Mater. Pharmaceuticals. 2024;17:1409. doi: 10.3390/ph17101409. PubMed DOI PMC

Azam S., Kim Y.S., Jakaria M., Yu Y.J., Ahn J.Y., Kim I.S., Choi D.K. Dioscorea nipponica Makino Rhizome Extract and Its Active Compound Dioscin Protect against Neuroinflammation and Scopolamine-Induced Memory Deficits. Int. J. Mol. Sci. 2022;23:9923. doi: 10.3390/ijms23179923. PubMed DOI PMC

Li S.Y., Zhou Y.L., He D.H., Liu W., Fan X.Z., Wang Q., Pan H.F., Cheng Y.X., Liu Y.Q. Centipeda minima extract exerts antineuroinflammatory effects via the inhibition of NF-κB signaling pathway. Phytomed. Int. J. Phytother. Phytopharm. 2020;67:153164. doi: 10.1016/j.phymed.2019.153164. PubMed DOI

Jeong Y.H., Li W., Go Y., Oh Y.C. Atractylodis Rhizoma Alba Attenuates Neuroinflammation in BV2 Microglia upon LPS Stimulation by Inducing HO-1 Activity and Inhibiting NF-κB and MAPK. Int. J. Mol. Sci. 2019;20:4015. doi: 10.3390/ijms20164015. PubMed DOI PMC

Kwon S.H., Ma S.X., Ko Y.H., Seo J.Y., Lee B.R., Lee T.H., Kim S.Y., Lee S.Y., Jang C.G. Vaccinium bracteatum Thunb. Exerts Anti-Inflammatory Activity by Inhibiting NF-κB Activation in BV-2 Microglial Cells. Biomol. Ther. 2016;24:543–551. doi: 10.4062/biomolther.2015.205. PubMed DOI PMC

Kwon S.H., Ma S.X., Hong S.I., Lee S.Y., Jang C.G. Lonicera japonica THUNB. Extract Inhibits Lipopolysaccharide-Stimulated Inflammatory Responses by Suppressing NF-κB Signaling in BV-2 Microglial Cells. J. Med. Food. 2015;18:762–775. doi: 10.1089/jmf.2014.3341. PubMed DOI PMC

Eom H.W., Park S.Y., Kim Y.H., Seong S.J., Jin M.L., Ryu E.Y., Kim M.J., Lee S.J. Bambusae Caulis in Taeniam modulates neuroprotective and anti-neuroinflammatory effects in hippocampal and microglial cells via HO-1- and Nrf-2-mediated pathways. Int. J. Mol. Med. 2012;30:1512–1520. doi: 10.3892/ijmm.2012.1128. PubMed DOI

Jung H.W., Yoon C.H., Park K.M., Han H.S., Park Y.K. Hexane fraction of Zingiberis Rhizoma Crudus extract inhibits the production of nitric oxide and proinflammatory cytokines in LPS-stimulated BV2 microglial cells via the NF-kappaB pathway. Food Chem. Toxicol. 2009;47:1190–1197. doi: 10.1016/j.fct.2009.02.012. PubMed DOI

Subedi L., Baek S.H., Kim S.Y. Genetically Engineered Resveratrol-Enriched Rice Inhibits Neuroinflammation in Lipopolysaccharide-Activated BV2 Microglia Via Downregulating Mitogen-Activated Protein Kinase-Nuclear Factor Kappa B Signaling Pathway. Oxid. Med. Cell Longev. 2018;2018:8092713. doi: 10.1155/2018/8092713. PubMed DOI PMC

Sen R., Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986;47:921–928. doi: 10.1016/0092-8674(86)90807-X. PubMed DOI

Sun E., Motolani A., Campos L., Lu T. The Pivotal Role of NF-kB in the Pathogenesis and Therapeutics of Alzheimer’s Disease. Int. J. Mol. Sci. 2022;23:8972. doi: 10.3390/ijms23168972. PubMed DOI PMC

Nennig S.E., Schank J.R. The Role of NFkB in Drug Addiction: Beyond Inflammation. Alcohol. Alcohol. 2017;52:172–179. doi: 10.1093/alcalc/agw098. PubMed DOI PMC

Yu H., Lin L., Zhang Z., Zhang H., Hu H. Targeting NF-kappaB pathway for the therapy of diseases: Mechanism and clinical study. Signal Transduct. Target. Ther. 2020;5:209. doi: 10.1038/s41392-020-00312-6. PubMed DOI PMC

Sun S.C. The non-canonical NF-kappaB pathway in immunity and inflammation. Nat. Rev. Immunol. 2017;17:545–558. doi: 10.1038/nri.2017.52. PubMed DOI PMC

Shih R.H., Wang C.Y., Yang C.M. NF-kappaB Signaling Pathways in Neurological Inflammation: A Mini Review. Front. Mol. Neurosci. 2015;8:77. doi: 10.3389/fnmol.2015.00077. PubMed DOI PMC

Zusso M., Lunardi V., Franceschini D., Pagetta A., Lo R., Stifani S., Frigo A.C., Giusti P., Moro S. Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-kB pathway. J. Neuroinflamm. 2019;16:148. doi: 10.1186/s12974-019-1538-9. PubMed DOI PMC

Shabab T., Khanabdali R., Moghadamtousi S.Z., Kadir H.A., Mohan G. Neuroinflammation pathways: A general review. Int. J. Neurosci. 2017;127:624–633. doi: 10.1080/00207454.2016.1212854. PubMed DOI

Glass C.K., Saijo K., Winner B., Marchetto M.C., Gage F.H. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140:918–934. doi: 10.1016/j.cell.2010.02.016. PubMed DOI PMC

Caetano-Silva M.E., Rund L.A., Vailati-Riboni M., Pacheco M.T.B., Johnson R.W. Copper-Binding Peptides Attenuate Microglia Inflammation through Suppression of NF-kB Pathway. Mol. Nutr. Food Res. 2021;65:e2100153. doi: 10.1002/mnfr.202100153. PubMed DOI PMC

Badenetti L., Manzoli R., Rubin M., Cozza G., Moro E. Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System. Int. J. Mol. Sci. 2023;24:6804. doi: 10.3390/ijms24076804. PubMed DOI PMC

Sandberg M., Patil J., D’Angelo B., Weber S.G., Mallard C. NRF2-regulation in brain health and disease: Implication of cerebral inflammation. Neuropharmacology. 2014;79:298–306. doi: 10.1016/j.neuropharm.2013.11.004. PubMed DOI PMC

Wei Z., Zhao J., Zhang L., Xia M. Cell-Based Assays to Identify Modulators of Nrf2/ARE Pathway. Methods Mol. Biol. 2022;2474:59–69. doi: 10.1007/978-1-0716-2213-1_7. PubMed DOI PMC

Sivandzade F., Prasad S., Bhalerao A., Cucullo L. NRF2 and NF-қB interplay in cerebrovascular and neurodegenerative disorders: Molecular mechanisms and possible therapeutic approaches. Redox Biol. 2019;21:101059. doi: 10.1016/j.redox.2018.11.017. PubMed DOI PMC

Dordoe C., Wang X., Lin P., Wang Z., Hu J., Wang D., Fang Y., Liang F., Ye S., Chen J., et al. Non-mitogenic fibroblast growth factor 1 protects against ischemic stroke by regulating microglia/macrophage polarization through Nrf2 and NF-kappaB pathways. Neuropharmacology. 2022;212:109064. doi: 10.1016/j.neuropharm.2022.109064. PubMed DOI

Zhang M., An C., Gao Y., Leak R.K., Chen J., Zhang F. Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection. Prog. Neurobiol. 2013;100:30–47. doi: 10.1016/j.pneurobio.2012.09.003. PubMed DOI PMC

Zhang Q., Liu J., Duan H., Li R., Peng W., Wu C. Activation of Nrf2/HO-1 signaling: An important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. J. Adv. Res. 2021;34:43–63. doi: 10.1016/j.jare.2021.06.023. PubMed DOI PMC

Zhou J., Zheng Q., Chen Z. The Nrf2 Pathway in Liver Diseases. Front. Cell Dev. Biol. 2022;10:826204. doi: 10.3389/fcell.2022.826204. PubMed DOI PMC

Taguchi K., Motohashi H., Yamamoto M. Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells. 2011;16:123–140. doi: 10.1111/j.1365-2443.2010.01473.x. PubMed DOI

Dayalan Naidu S., Muramatsu A., Saito R., Asami S., Honda T., Hosoya T., Itoh K., Yamamoto M., Suzuki T., Dinkova-Kostova A.T. C151 in KEAP1 is the main cysteine sensor for the cyanoenone class of NRF2 activators, irrespective of molecular size or shape. Sci. Rep. 2018;8:8037. doi: 10.1038/s41598-018-26269-9. PubMed DOI PMC

Song X., Long D. Nrf2 and Ferroptosis: A New Research Direction for Neurodegenerative Diseases. Front. Neurosci. 2020;14:267. doi: 10.3389/fnins.2020.00267. PubMed DOI PMC

Mohan S., Gupta D. Crosstalk of toll-like receptors signaling and Nrf2 pathway for regulation of inflammation. Biomed. Pharmacother. 2018;108:1866–1878. doi: 10.1016/j.biopha.2018.10.019. PubMed DOI

Cores Á., Piquero M., Villacampa M., León R., Menéndez J.C. NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases. Biomolecules. 2020;10:904. doi: 10.3390/biom10060904. PubMed DOI PMC

Gan L., Johnson J.A. Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases. Biochim. Biophys. Acta. 2014;1842:1208–1218. doi: 10.1016/j.bbadis.2013.12.011. PubMed DOI

He W.J., Lv C.H., Chen Z., Shi M., Zeng C.X., Hou D.X., Qin S. The Regulatory Effect of Phytochemicals on Chronic Diseases by Targeting Nrf2-ARE Signaling Pathway. Antioxidants. 2023;12:236. doi: 10.3390/antiox12020236. PubMed DOI PMC

Amoroso R., Maccallini C., Bellezza I. Activators of Nrf2 to Counteract Neurodegenerative Diseases. Antioxidants. 2023;12:778. doi: 10.3390/antiox12030778. PubMed DOI PMC

Seok J.K., Kang H.C., Cho Y.Y., Lee H.S., Lee J.Y. Therapeutic regulation of the NLRP3 inflammasome in chronic inflammatory diseases. Arch. Pharm. Res. 2021;44:16–35. doi: 10.1007/s12272-021-01307-9. PubMed DOI PMC

Malik A., Kanneganti T.D. Inflammasome activation and assembly at a glance. J. Cell Sci. 2017;130:3955–3963. doi: 10.1242/jcs.207365. PubMed DOI PMC

Swanson K.V., Deng M., Ting J.P. The NLRP3 inflammasome: Molecular activation and regulation to therapeutics. Nat. Rev. Immunol. 2019;19:477–489. doi: 10.1038/s41577-019-0165-0. PubMed DOI PMC

Guo H., Callaway J.B., Ting J.P. Inflammasomes: Mechanism of action, role in disease, and therapeutics. Nat. Med. 2015;21:677–687. doi: 10.1038/nm.3893. PubMed DOI PMC

Bulte D., Rigamonti C., Romano A., Mortellaro A. Inflammasomes: Mechanisms of Action and Involvement in Human Diseases. Cells. 2023;12:1766. doi: 10.3390/cells12131766. PubMed DOI PMC

Fu J., Wu H. Structural Mechanisms of NLRP3 Inflammasome Assembly and Activation. Annu. Rev. Immunol. 2023;41:301–316. doi: 10.1146/annurev-immunol-081022-021207. PubMed DOI PMC

Song N., Li T. Regulation of NLRP3 Inflammasome by Phosphorylation. Front. Immunol. 2018;9:2305. doi: 10.3389/fimmu.2018.02305. PubMed DOI PMC

Wu N., Zheng C., Xu J., Ma S., Jia H., Yan M., An F., Zhou Y., Qi J., Bian H. Race between virus and inflammasomes: Inhibition or escape, intervention and therapy. Front. Cell Infect. Microbiol. 2023;13:1173505. doi: 10.3389/fcimb.2023.1173505. PubMed DOI PMC

Anderson F.L., Biggs K.E., Rankin B.E., Havrda M.C. NLRP3 inflammasome in neurodegenerative disease. Transl. Res. 2023;252:21–33. doi: 10.1016/j.trsl.2022.08.006. PubMed DOI PMC

Paik S., Kim J.K., Silwal P., Sasakawa C., Jo E.K. An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell Mol. Immunol. 2021;18:1141–1160. doi: 10.1038/s41423-021-00670-3. PubMed DOI PMC

Zhan X., Li Q., Xu G., Xiao X., Bai Z. The mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors. Front. Immunol. 2022;13:1109938. doi: 10.3389/fimmu.2022.1109938. PubMed DOI PMC

Biasizzo M., Kopitar-Jerala N. Interplay Between NLRP3 Inflammasome and Autophagy. Front. Immunol. 2020;11:591803. doi: 10.3389/fimmu.2020.591803. PubMed DOI PMC

Kelley N., Jeltema D., Duan Y., He Y. The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci. 2019;20:3328. doi: 10.3390/ijms20133328. PubMed DOI PMC

Pellegrini C., Antonioli L., Lopez-Castejon G., Blandizzi C., Fornai M. Canonical and Non-Canonical Activation of NLRP3 Inflammasome at the Crossroad between Immune Tolerance and Intestinal Inflammation. Front. Immunol. 2017;8:36. doi: 10.3389/fimmu.2017.00036. PubMed DOI PMC

Zhao C., Zhao W. NLRP3 Inflammasome-A Key Player in Antiviral Responses. Front. Immunol. 2020;11:211. doi: 10.3389/fimmu.2020.00211. PubMed DOI PMC

Zito G., Buscetta M., Cimino M., Dino P., Bucchieri F., Cipollina C. Cellular Models and Assays to Study NLRP3 Inflammasome Biology. Int. J. Mol. Sci. 2020;21:4294. doi: 10.3390/ijms21124294. PubMed DOI PMC

Lin S., Mei X. Role of NLRP3 Inflammasomes in Neuroinflammation Diseases. Eur. Neurol. 2020;83:576–580. doi: 10.1159/000509798. PubMed DOI

Han Q.Q., Le W. NLRP3 Inflammasome-Mediated Neuroinflammation and Related Mitochondrial Impairment in Parkinson’s Disease. Neurosci. Bull. 2023;39:832–844. doi: 10.1007/s12264-023-01023-y. PubMed DOI PMC

Lu R., Zhang L., Yang X. Interaction between autophagy and the NLRP3 inflammasome in Alzheimer’s and Parkinson’s disease. Front. Aging Neurosci. 2022;14:1018848. doi: 10.3389/fnagi.2022.1018848. PubMed DOI PMC

Soraci L., Gambuzza M.E., Biscetti L., Laganà P., Lo Russo C., Buda A., Barresi G., Corsonello A., Lattanzio F., Lorello G., et al. Toll-like receptors and NLRP3 inflammasome-dependent pathways in Parkinson’s disease: Mechanisms and therapeutic implications. J. Neurol. 2023;270:1346–1360. doi: 10.1007/s00415-022-11491-3. PubMed DOI PMC

Su Q., Ng W.L., Goh S.Y., Gulam M.Y., Wang L.F., Tan E.K., Ahn M., Chao Y.X. Targeting the inflammasome in Parkinson’s disease. Front. Aging Neurosci. 2022;14:957705. doi: 10.3389/fnagi.2022.957705. PubMed DOI PMC

Barczuk J., Siwecka N., Lusa W., Rozpedek-Kaminska W., Kucharska E., Majsterek I. Targeting NLRP3-Mediated Neuroinflammation in Alzheimer’s Disease Treatment. Int. J. Mol. Sci. 2022;23:8979. doi: 10.3390/ijms23168979. PubMed DOI PMC

Severini C., Barbato C., Di Certo M.G., Gabanella F., Petrella C., Di Stadio A., de Vincentiis M., Polimeni A., Ralli M., Greco A. Alzheimer’s Disease: New Concepts on the Role of Autoimmunity and NLRP3 Inflammasome in the Pathogenesis of the Disease. Curr. Neuropharmacol. 2021;19:498–512. doi: 10.2174/1570159X18666200621204546. PubMed DOI PMC

Liang T., Zhang Y., Wu S., Chen Q., Wang L. The Role of NLRP3 Inflammasome in Alzheimer’s Disease and Potential Therapeutic Targets. Front. Pharmacol. 2022;13:845185. doi: 10.3389/fphar.2022.845185. PubMed DOI PMC

Yang Z., Liu J., Wei S., Deng J., Feng X., Liu S., Liu M. A novel strategy for bioactive natural products targeting NLRP3 inflammasome in Alzheimer’s disease. Front. Pharmacol. 2022;13:1077222. doi: 10.3389/fphar.2022.1077222. PubMed DOI PMC

Deng C., Cai X., Jin K., Wang Q. Editorial: The NLRP3 inflammasome-mediated neuroinflammation and its related mitochondrial impairment in neurodegeneration. Front. Aging Neurosci. 2022;14:1118281. doi: 10.3389/fnagi.2022.1118281. PubMed DOI PMC

Zhu X., Liu H., Wang D., Guan R., Zou Y., Li M., Zhang J., Chen J. NLRP3 deficiency protects against hypobaric hypoxia induced neuroinflammation and cognitive dysfunction. Ecotoxicol. Environ. Saf. 2023;255:114828. doi: 10.1016/j.ecoenv.2023.114828. PubMed DOI

Yu Q., Zhao T., Liu M., Cao D., Li J., Li Y., Xia M., Wang X., Zheng T., Liu C., et al. Targeting NLRP3 Inflammasome in Translational Treatment of Nervous System Diseases: An Update. Front. Pharmacol. 2021;12:707696. doi: 10.3389/fphar.2021.707696. PubMed DOI PMC

Sarapultsev A., Gusev E., Komelkova M., Utepova I., Luo S., Hu D. JAK-STAT signaling in inflammation and stress-related diseases: Implications for therapeutic interventions. Mol. Biomed. 2023;4:40. doi: 10.1186/s43556-023-00151-1. PubMed DOI PMC

Cardona K., Medina J., Orrego-Cardozo M., Restrepo de Mejía F., Elcoroaristizabal X., Naranjo Galvis C.A. Inflammatory gene expression profiling in peripheral blood from patients with Alzheimer’s disease reveals key pathways and hub genes with potential diagnostic utility: A preliminary study. PeerJ. 2021;9:e12016. doi: 10.7717/peerj.12016. PubMed DOI PMC

Jain M., Singh M.K., Shyam H., Mishra A., Kumar S., Kumar A., Kushwaha J. Role of JAK/STAT in the Neuroinflammation and its Association with Neurological Disorders. Ann. Neurosci. 2021;28:191–200. doi: 10.1177/09727531211070532. PubMed DOI PMC

Oh S.L., Zhou M., Chin E.W.M., Amarnath G., Cheah C.H., Ng K.P., Kandiah N., Goh E.L.K., Chiam K.H. Alzheimer’s Disease Blood Biomarkers Associated With Neuroinflammation as Therapeutic Targets for Early Personalized Intervention. Front. Digit. Health. 2022;4:875895. doi: 10.3389/fdgth.2022.875895. PubMed DOI PMC

Varma V.R., Desai R.J., Navakkode S., Wong L.W., Anerillas C., Loeffler T., Schilcher I., Mahesri M., Chin K., Horton D.B., et al. Hydroxychloroquine lowers Alzheimer’s disease and related dementias risk and rescues molecular phenotypes related to Alzheimer’s disease. Mol. Psychiatry. 2023;28:1312–1326. doi: 10.1038/s41380-022-01912-0. PubMed DOI PMC

Rusek M., Smith J., El-Khatib K., Aikins K., Czuczwar S.J., Pluta R. The Role of the JAK/STAT Signaling Pathway in the Pathogenesis of Alzheimer’s Disease: New Potential Treatment Target. Int. J. Mol. Sci. 2023;24:864. doi: 10.3390/ijms24010864. PubMed DOI PMC

Nevado-Holgado A.J., Ribe E., Thei L., Furlong L., Mayer M.A., Quan J., Richardson J.C., Cavanagh J., Consortium N., Lovestone S. Genetic and Real-World Clinical Data, Combined with Empirical Validation, Nominate Jak-Stat Signaling as a Target for Alzheimer’s Disease Therapeutic Development. Cells. 2019;8:425. doi: 10.3390/cells8050425. PubMed DOI PMC

Porro C., Cianciulli A., Trotta T., Lofrumento D.D., Panaro M.A. Curcumin Regulates Anti-Inflammatory Responses by JAK/STAT/SOCS Signaling Pathway in BV-2 Microglial Cells. Biology. 2019;8:51. doi: 10.3390/biology8030051. PubMed DOI PMC

Yan Z., Gibson S.A., Buckley J.A., Qin H., Benveniste E.N. Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases. Clin. Immunol. 2018;189:4–13. doi: 10.1016/j.clim.2016.09.014. PubMed DOI PMC

Qin H., Buckley J.A., Li X., Liu Y., Fox T.H., 3rd, Meares G.P., Yu H., Yan Z., Harms A.S., Li Y., et al. Inhibition of the JAK/STAT Pathway Protects Against α-Synuclein-Induced Neuroinflammation and Dopaminergic Neurodegeneration. J Neurosci. 2016;36:5144–5159. doi: 10.1523/JNEUROSCI.4658-15.2016. PubMed DOI PMC

Hu X., Li J., Fu M., Zhao X., Wang W. The JAK/STAT signaling pathway: From bench to clinic. Signal Transduct. Target. Ther. 2021;6:402. doi: 10.1038/s41392-021-00791-1. PubMed DOI PMC

Vidal-Itriago A., Radford R.A., Aramideh J.A., Maurel C., Scherer N.M., Don E.K., Lee A., Chung R.S., Graeber M.B., Morsch M. Microglia morphophysiological diversity and its implications for the CNS. Front. Front. Immunol. Immunol. 2022;13:997786. doi: 10.3389/fimmu.2022.997786. PubMed DOI PMC

Gullotta G.S., Costantino G., Sortino M.A., Spampinato S.F. Microglia and the blood–brain barrier: An external player in acute and chronic neuroinflammatory conditions. Int. J. Mol. Sci. 2023;24:9144. doi: 10.3390/ijms24119144. PubMed DOI PMC

Son Y., Yeo I.-J., Hong J.-T., Eo S.-K., Lee D., Kim K. Side-Chain Immune Oxysterols Induce Neuroinflammation by Activating Microglia. Int. J. Mol. Sci. 2023;24:15288. doi: 10.3390/ijms242015288. PubMed DOI PMC

Sun Y., Che J., Zhang J. Emerging non-proinflammatory roles of microglia in healthy and diseased brains. Brain Res. Bull. 2023;199:110664. doi: 10.1016/j.brainresbull.2023.110664. PubMed DOI

Zhang W., Jiang J., Xu Z., Yan H., Tang B., Liu C., Chen C., Meng Q. Microglia-containing human brain organoids for the study of brain development and pathology. Mol. Psychiatry. 2023;28:96–107. doi: 10.1038/s41380-022-01892-1. PubMed DOI PMC

Colonna M., Butovsky O. Microglia function in the central nervous system during health and neurodegeneration. Annu. Rev. Immunol. 2017;35:441–468. doi: 10.1146/annurev-immunol-051116-052358. PubMed DOI PMC

Matsudaira T., Prinz M. Life and death of microglia: Mechanisms governing microglial states and fates. Immunol. Lett. 2022;245:51–60. doi: 10.1016/j.imlet.2022.04.001. PubMed DOI

Wright-Jin E.C., Gutmann D.H. Microglia as dynamic cellular mediators of brain function. Trends Mol. Med. 2019;25:967–979. doi: 10.1016/j.molmed.2019.08.013. PubMed DOI PMC

Costa J., Martins S., Ferreira P.A., Cardoso A.M., Guedes J.R., Peça J., Cardoso A.L. The old guard: Age-related changes in microglia and their consequences. Mech. Ageing Dev. 2021;197:111512. doi: 10.1016/j.mad.2021.111512. PubMed DOI

Al-Onaizi M., Al-Khalifah A., Qasem D., ElAli A. Role of microglia in modulating adult neurogenesis in health and neurodegeneration. Int. J. Mol. Sci. 2020;21:6875. doi: 10.3390/ijms21186875. PubMed DOI PMC

D’Alessandro G., Marrocco F., Limatola C. Microglial cells: Sensors for neuronal activity and microbiota-derived molecules. Front. Immunol. 2022;13:1011129. doi: 10.3389/fimmu.2022.1011129. PubMed DOI PMC

Zhang L., Wang Y., Liu T., Mao Y., Peng B. Novel microglia-based therapeutic approaches to neurodegenerative disorders. Neurosci. Bull. 2023;39:491–502. doi: 10.1007/s12264-022-01013-6. PubMed DOI PMC

Liu W., Taso O., Wang R., Bayram S., Graham A.C., Garcia-Reitboeck P., Mallach A., Andrews W.D., Piers T.M., Botia J.A. Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions. Human. Mol. Genet. 2020;29:3224–3248. doi: 10.1093/hmg/ddaa209. PubMed DOI PMC

Strizova Z., Benesova I., Bartolini R., Novysedlak R., Cecrdlova E., Foley L.K., Striz I. M1/M2 macrophages and their overlaps—Myth or reality? Clin. Sci. 2023;137:1067–1093. doi: 10.1042/CS20220531. PubMed DOI PMC

Gao C., Jiang J., Tan Y., Chen S. Microglia in neurodegenerative diseases: Mechanism and potential therapeutic targets. Signal Transduct. Target. Ther. 2023;8:359. doi: 10.1038/s41392-023-01588-0. PubMed DOI PMC

Li J., Shui X., Sun R., Wan L., Zhang B., Xiao B., Luo Z. Microglial Phenotypic Transition: Signaling Pathways and Influencing Modulators Involved in Regulation in Central Nervous System Diseases. Front. Cell. Neurosci. 2021;15:736310. doi: 10.3389/fncel.2021.736310. PubMed DOI PMC

Lis-López L., Bauset C., Seco-Cervera M., Cosín-Roger J. Is the Macrophage Phenotype Determinant for Fibrosis Development? Biomedicines. 2021;9:1747. doi: 10.3390/biomedicines9121747. PubMed DOI PMC

Gomes C., Ferreira R., George J., Sanches R., Rodrigues D.I., Gonçalves N., Cunha R.A. Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A2A receptor-dependent manner: A2A receptor blockade prevents BDNF release and proliferation of microglia. J. Neuroinflamm. 2013;10:780. doi: 10.1186/1742-2094-10-16. PubMed DOI PMC

Russo C., Valle M.S., Russo A., Malaguarnera L. The interplay between ghrelin and microglia in neuroinflammation: Implications for obesity and neurodegenerative diseases. Int. J. Mol. Sci. 2022;23:13432. doi: 10.3390/ijms232113432. PubMed DOI PMC

Liu L., Tong F., Li H., Bin Y., Ding P., Peng L., Liu Z., Dong X. Maturation, morphology, and function: The decisive role of intestinal flora on microglia: A review. J. Integr. Neurosci. 2023;22:70. doi: 10.31083/j.jin2203070. PubMed DOI

Ng P.Y., McNeely T.L., Baker D.J. Untangling senescent and damage-associated microglia in the aging and diseased brain. FEBS J. 2023;290:1326–1339. doi: 10.1111/febs.16315. PubMed DOI PMC

Umpierre A.D., Wu L.J. How microglia sense and regulate neuronal activity. Glia. 2021;69:1637–1653. doi: 10.1002/glia.23961. PubMed DOI PMC

Hristovska I., Robert M., Combet K., Honnorat J., Comte J., Pascual O. Sleep decreases neuronal activity control of microglial dynamics in mice. Nat. Commun. 2022;13:6273. doi: 10.1038/s41467-022-34035-9. PubMed DOI PMC

Ikegami A., Kato D., Wake H. Microglial process dynamics depend on astrocyte and synaptic activity. Nagoya J. Med. Sci. 2023;85:772. PubMed PMC

Ahn K., Lee S.J., Mook-Jung I. White matter-associated microglia: New players in brain aging and neurodegenerative diseases. Ageing Res. Rev. 2022;75:101574. doi: 10.1016/j.arr.2022.101574. PubMed DOI

Sun N., Victor M.B., Park Y.P., Xiong X., Scannail A.N., Leary N., Prosper S., Viswanathan S., Luna X., Boix C.A., et al. Human microglial state dynamics in Alzheimer’s disease progression. Cell. 2023;186:4386–4403.e29. doi: 10.1016/j.cell.2023.08.037. PubMed DOI PMC

Kelly R., Joers V., Tansey M.G., McKernan D.P., Dowd E. Microglial Phenotypes and Their Relationship to the Cannabinoid System: Therapeutic Implications for Parkinson’s Disease. Molecules. 2020;25:453. doi: 10.3390/molecules25030453. PubMed DOI PMC

Tanaka M., Vécsei L. Editorial of Special Issue ‘Dissecting Neurological and Neuropsychiatric Diseases: Neurodegeneration and Neuroprotection’. J. Mol. Sci. 2022;23:13. doi: 10.3390/ijms23136991. PubMed DOI PMC

Harry G.J. Microglia in Neurodegenerative Events-An Initiator or a Significant Other? Int. J. Mol. Sci. 2021;22:5818. doi: 10.3390/ijms22115818. PubMed DOI PMC

Tofaris G.K. Initiation and progression of α-synuclein pathology in Parkinson’s disease. Cell Mol. Life Sci. 2022;79:210. doi: 10.1007/s00018-022-04240-2. PubMed DOI PMC

Toni M. Special Issue “Neurobiology of Protein Synuclein”. Int. J. Mol. Sci. 2024;25:3223. doi: 10.3390/ijms25063223. PubMed DOI PMC

Badanjak K., Fixemer S., Smajić S., Skupin A., Grünewald A. The Contribution of Microglia to Neuroinflammation in Parkinson’s Disease. Int. J. Mol. Sci. 2021;22:4676. doi: 10.3390/ijms22094676. PubMed DOI PMC

Basellini M.J., Kothuis J.M., Comincini A., Pezzoli G., Cappelletti G., Mazzetti S. Pathological Pathways and Alpha-Synuclein in Parkinson’s Disease: A View from the Periphery. Front. Biosci. 2023;28:33. doi: 10.31083/j.fbl2802033. PubMed DOI

Xu Y., Li Y., Wang C., Han T., Liu H., Sun L., Hong J., Hashimoto M., Wei J. The reciprocal interactions between microglia and T cells in Parkinson’s disease: A double-edged sword. J. Neuroinflamm. 2023;20:33. doi: 10.1186/s12974-023-02723-y. PubMed DOI PMC

Yan Y.Q., Zheng R., Liu Y., Ruan Y., Lin Z.H., Xue N.J., Chen Y., Zhang B.R., Pu J.L. Parkin regulates microglial NLRP3 and represses neurodegeneration in Parkinson’s disease. Aging Cell. 2023;22:e13834. doi: 10.1111/acel.13834. PubMed DOI PMC

Yang J., Hamade M., Wu Q., Wang Q., Axtell R., Giri S., Mao-Draayer Y. Current and Future Biomarkers in Multiple Sclerosis. Int. J. Mol. Sci. 2022;23:5877. doi: 10.3390/ijms23115877. PubMed DOI PMC

Charabati M., Wheeler M.A., Weiner H.L., Quintana F.J. Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting. Cell. 2023;186:1309–1327. doi: 10.1016/j.cell.2023.03.008. PubMed DOI PMC

Mey G.M., Mahajan K.R., DeSilva T.M. Neurodegeneration in multiple sclerosis. WIREs Mech. Dis. 2023;15:e1583. doi: 10.1002/wsbm.1583. PubMed DOI PMC

Ren J., Dai C., Zhou X., Barnes J.A., Chen X., Wang Y., Yuan L., Shingu T., Heimberger A.B., Chen Y., et al. Qki is an essential regulator of microglial phagocytosis in demyelination. J. Exp. Med. 2021;218:e20190348. doi: 10.1084/jem.20190348. PubMed DOI PMC

Zhang X., Chen F., Sun M., Wu N., Liu B., Yi X., Ge R., Fan X. Microglia in the context of multiple sclerosis. Front. Neurol. 2023;14:1157287. doi: 10.3389/fneur.2023.1157287. PubMed DOI PMC

Yu Z., Fang X., Liu W., Sun R., Zhou J., Pu Y., Zhao M., Sun D., Xiang Z., Liu P., et al. Microglia Regulate Blood-Brain Barrier Integrity via MiR-126a-5p/MMP9 Axis during Inflammatory Demyelination. Adv. Sci. 2022;9:e2105442. doi: 10.1002/advs.202105442. PubMed DOI PMC

Tanaka M., Szabó Á., Vécsei L. Preclinical modeling in depression and anxiety: Current challenges and future research directions. Adv. Clin. Exp. Med. Off. Organ Wroc. Med. Univ. 2023;32:505–509. doi: 10.17219/acem/165944. PubMed DOI PMC

Nunes Y.C., Mendes N.M., Pereira de Lima E., Chehadi A.C., Lamas C.B., Haber J.F.S., Dos Santos Bueno M., Araújo A.C., Catharin V.C.S., Detregiachi C.R.P., et al. Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence. Nutrients. 2024;16:2721. doi: 10.3390/nu16162721. PubMed DOI PMC

Wróbel-Biedrawa D., Podolak I. Anti-Neuroinflammatory Effects of Adaptogens: A Mini-Review. Molecules. 2024;29:866. doi: 10.3390/molecules29040866. PubMed DOI PMC