Prion' is a term used to describe a protein infectious particle responsible for several neurodegenerative diseases in mammals, e.g., Creutzfeldt-Jakob disease. The novelty is that it is protein based infectious agent not involving a nucleic acid genome as found in viruses and bacteria. Prion disorders exhibit, in part, incubation periods, neuronal loss, and induce abnormal folding of specific normal cellular proteins due to enhancing reactive oxygen species associated with mitochondria energy metabolism. These agents may also induce memory, personality and movement abnormalities as well as depression, confusion and disorientation. Interestingly, some of these behavioral changes also occur in COVID-19 and mechanistically include mitochondrial damage caused by SARS-CoV-2 and subsequenct production of reactive oxygen species. Taken together, we surmise, in part, long COVID may involve the induction of spontaneous prion emergence, especially in individuals susceptible to its origin may thus explain some of its manesfestions post-acute viral infection.

1st Faculty of Medicine Department of Psychiatry of the 1st Faculty of Medicine and General Teaching Hospital Charles University Prague 120 00 Prague 2 Ke Karlovu 11 Prague Czech Republic

Department of Psychology University of New York Prague 120 00 Prague 2 Londýnská 41 Prague Czech Republic

Zobrazit více v PubMed

Benz D, Cadet P, Mantione K, Zhu W, Stefano GB. Tonal nitric oxide and health: a free radical and a scavenger of free radicals. Med Sci Monit. 2002;8(1):1–4. PubMed

Choi SI, Ju WK, Choi EK, Kim J, Lea HZ, Carp RI, Wisniewski HM, Kim YS. Mitochondrial dysfunction induced by oxidative stress in the brains of hamsters infected with the 263 K scrapie agent. Acta Neuropathol. 1998;96(3):279–286. doi: 10.1007/s004010050895. PubMed DOI

Colini Baldeschi A, Zattoni M, Vanni S, Nikolic L, Ferracin C, La Sala G, Summa M, Bertorelli R, Bertozzi SM, Giachin G, Carloni P, Bolognesi ML, De Vivo M, Legname G. Innovative non-PrP-targeted drug strategy designed to enhance prion clearance. J Med Chem. 2022;65(13):8998–9010. doi: 10.1021/acs.jmedchem.2c00205. PubMed DOI PMC

De Armond SJ, Bouzamondo E. Fundamentals of prion biology and diseases. Toxicology. 2002;181–182:9–16. doi: 10.1016/s0300-483x(02)00249-4. PubMed DOI

de la Torre JC, Stefano GB. Evidence that Alzheimer’s disease is a microvascular disorder: the role of constitutive nitric oxide. Brain ResRev. 2000;34:119–136. doi: 10.1016/S0165-0173(00)00043-6. PubMed DOI

Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, Lange F, Andersson JLR, Griffanti L, Duff E, Jbabdi S, Taschler B, Keating P, Winkler AM, Collins R, Matthews PM, Allen N, Miller KL, Nichols TE, Smith SM. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature. 2022 doi: 10.1038/s41586-022-04569-5. PubMed DOI PMC

Dutta S, Das N, Mukherjee P. Picking up a fight: fine tuning mitochondrial innate immune defenses against RNA viruses. Front Microbiol. 2020;11:1990. doi: 10.3389/fmicb.2020.01990. PubMed DOI PMC

Faris RM, Ward RA, Sturdevant A, Priola DE, S.A. Mitochondrial respiration is impaired during late-stage hamster prion infection. J Virol. 2017;91(18):1–15. doi: 10.1128/JVI.00524-17. PubMed DOI PMC

Hara H, Chida J, Uchiyama K, Pasiana AD, Takahashi E, Kido H, Sakaguchi S. Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells. Sci Rep. 2021;11(1):10109. doi: 10.1038/s41598-021-89586-6. PubMed DOI PMC

Islam MT. Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res. 2017;39(1):73–82. doi: 10.1080/01616412.2016.1251711. PubMed DOI

Kim MJ, Kim HJ, Jang B, Kim HJ, Mostafa MN, Park SJ, Kim YS, Choi EK. Impairment of neuronal mitochondrial quality control in prion-induced neurodegeneration. Cells. 2022 doi: 10.3390/cells11172744. PubMed DOI PMC

Liang G, Bushman FD. The human virome: assembly, composition and host interactions. Nat Rev Microbiol. 2021;19(8):514–527. doi: 10.1038/s41579-021-00536-5. PubMed DOI PMC

McKintosh E, Tabrizi SJ, Collinge J. Prion diseases. J Neurovirol. 2003;9(2):183–193. doi: 10.1080/13550280390194082. PubMed DOI

Moore RA, Sturdevant DE, Chesebro B, Priola SA. Proteomics analysis of amyloid and nonamyloid prion disease phenotypes reveals both common and divergent mechanisms of neuropathogenesis. J Proteome Res. 2014;13(11):4620–4634. doi: 10.1021/pr500329w. PubMed DOI PMC

Shkoporov AN, Hill C. Bacteriophages of the human gut: the “Known Unknown” of the microbiome. Cell Host Microbe. 2019;25(2):195–209. doi: 10.1016/j.chom.2019.01.017. PubMed DOI

Singh KK, Chaubey G, Chen JY, Suravajhala P. Decoding SARS-CoV-2 hijacking of host mitochondria in COVID-19 pathogenesis. Am J Physiol Cell Physiol. 2020;319(2):C258–C267. doi: 10.1152/ajpcell.00224.2020. PubMed DOI PMC

Stefano GB, Kream RM. Mitochondrial DNA heteroplasmy as an informational reservoir dynamically linked to metabolic and immunological processes associated with COVID-19 neurological disorders. Cell Mol Neurobiol. 2022;42(1):99–107. doi: 10.1007/s10571-021-01117-z. PubMed DOI PMC

Stefano GB, Kream RM. Viruses broaden the definition of life by genomic incorporation of artificial intelligence and machine learning processes. Curr Neuropharmacol. 2022;20:1888–1893. doi: 10.2174/1570159X20666220420121746. PubMed DOI PMC

Stefano GB, Esch T, Ptacek R, Kream RM. Dysregulation of nitric oxide signaling in microglia: multiple points of functional convergence in the complex pathophysiology of Alzheimer’s disease. Med Sci Monit. 2020 doi: 10.12659/MSM.927739. PubMed DOI PMC

Stefano GB, Buttiker P, Weissenberger S, Martin A, Ptacek R, Kream RM. Editorial: the pathogenesis of long-term neuropsychiatric COVID-19 and the role of microglia, mitochondria, and persistent neuroinflammation: a hypothesis. Med Sci Monit. 2021;27:e933015. doi: 10.12659/MSM.933015. PubMed DOI PMC

Stefano GB, Buttiker P, Weissenberger S, Ptacek R, Wang F, Esch T, Bilfinger TV, Raboch J, Kream RM. Biomedical perspectives of acute and chronic neurological and neuropsychiatric sequelae of COVID-19. Curr Neuropharmacol. 2022;20(6):1229–1240. doi: 10.2174/1570159X20666211223130228. PubMed DOI PMC

Stein SR, Ramelli SC, Grazioli A, Chung JY, Singh M, Yinda CK, Winkler CW, Sun J, Dickey JM, Ylaya K, Ko SH, Platt AP, Burbelo PD, Quezado M, Pittaluga S, Purcell M, Munster VJ, Belinky F, Ramos-Benitez MJ, Boritz EA, Lach IA, Herr DL, Rabin J, Saharia KK, Madathil RJ, Tabatabai A, Soherwardi S, McCurdy MT, Consortium NC-A. Peterson KE, Cohen JI, de Wit E, Vannella KM, Hewitt SM, Kleiner DE, Chertow DS. SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature. 2022;612(7941):758–763. doi: 10.1038/s41586-022-05542-y. PubMed DOI PMC

Tian C, Dong X. The structure of prion: is it enough for interpreting the diverse phenotypes of prion diseases? Acta Biochim Biophys Sin (shanghai) 2013;45(6):429–434. doi: 10.1093/abbs/gmt021. PubMed DOI

Ulland TK, Song WM, Huang SC, Ulrich JD, Sergushichev A, Beatty WL, Loboda AA, Zhou Y, Cairns NJ, Kambal A, Loginicheva E, Gilfillan S, Cella M, Virgin HW, Unanue ER, Wang Y, Artyomov MN, Holtzman DM, Colonna M. TREM2 maintains microglial metabolic fitness in Alzheimer’s disease. Cell. 2017;170(4):649–663 e613. doi: 10.1016/j.cell.2017.07.023. PubMed DOI PMC

Wang F, Kream RM, Stefano GB. Long-term respiratory and neurological sequelae of COVID-19. Med Sci Monit. 2020;26:e928996. doi: 10.12659/MSM.928996. PubMed DOI PMC

Wei W, Schon KR, Elgar G, Orioli A, Tanguy M, Giess A, Tischkowitz M, Caulfield MJ, Chinnery PF. Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes. Nature. 2022 doi: 10.1038/s41586-022-05288-7. PubMed DOI PMC

Wu KE, Fazal FM, Parker KR, Zou J, Chang HY. RNA-GPS Predicts SARS-CoV-2 RNA residency to host mitochondria and nucleolus. Cell Syst. 2020;11(1):102–108 e103. doi: 10.1016/j.cels.2020.06.008. PubMed DOI PMC

Xu E, Xie Y, Al-Aly Z. Long-term neurologic outcomes of COVID-19. Nat Med. 2022;28(11):2406–2415. doi: 10.1038/s41591-022-02001-z. PubMed DOI PMC

Yardeni T, Tanes CE, Bittinger K, Mattei LM, Schaefer PM, Singh LN, Wu GD, Murdock DG, Wallace DC. Host mitochondria influence gut microbiome diversity: a role for ROS. Sci Signal. 2019 doi: 10.1126/scisignal.aaw3159. PubMed DOI

Young MJ, O'Hare M, Matiello M, Schmahmann JD. Creutzfeldt-Jakob disease in a man with COVID-19: SARS-CoV-2-accelerated neurodegeneration? Brain Behav Immun. 2020;89:601–603. doi: 10.1016/j.bbi.2020.07.007. PubMed DOI PMC

Zambrano K, Barba D, Castillo K, Robayo P, Arizaga E, Caicedo A, Gavilanes AWD. A new hope: mitochondria, a critical factor in the war against prions. Mitochondrion. 2022;65:113–123. doi: 10.1016/j.mito.2022.05.004. PubMed DOI

Zattoni M, Mearelli M, Vanni S, Colini Baldeschi A, Tran TH, Ferracin C, Catania M, Moda F, Di Fede G, Giaccone G, Tagliavini F, Zanusso G, Ironside JW, Ferrer I, Legname G. Serpin signatures in prion and Alzheimer’s diseases. Mol Neurobiol. 2022;59(6):3778–3799. doi: 10.1007/s12035-022-02817-3. PubMed DOI PMC

Zhou T, Wu J, Zeng Y, Li J, Yan J, Meng W, Han H, Feng F, He J, Zhao S, Zhou P, Wu Y, Yang Y, Han R, Jin W, Li X, Yang Y. Li X (2022) SARS-CoV-2 triggered oxidative stress and abnormal energy metabolism in gut microbiota. MedComm. 2020;3(1):e112. doi: 10.1002/mco2.112. PubMed DOI PMC

Quantum Computing and the Future of Neurodegeneration and Mental Health Research