Neurodegenerative diseases are pathologies of the central and peripheral nervous systems characterized by loss of brain functions and problems in movement which occur due to the slow and progressive degeneration of cellular elements. Several neurodegenerative diseases are known such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and many studies on the molecular mechanisms underlying these pathologies have been conducted. Altered functions of some key proteins and the presence of intraneuronal aggregates have been identified as responsible for the development of the diseases. Interestingly, the formation of the SNARE complex has been discovered to be fundamental for vesicle fusion, vesicle recycling and neurotransmitter release. Indeed, inhibition of the formation of the SNARE complex, defects in the SNARE-dependent exocytosis and altered regulation of SNARE-mediated vesicle fusion have been associated with neurodegeneration. In this review, the biological aspects of neurodegenerative diseases and the role of SNARE proteins in relation to the onset of these pathologies are described.

• Klíčová slova
• ALS, Alzheimer’s disease, Parkinson’s disease, SNAP-25, SNAREs, VAMP2, neurodegenerative disease, syn1,
• MeSH
• exocytóza * MeSH
• fúze membrán * MeSH
• lidé MeSH
• nervový přenos * MeSH
• neurodegenerativní nemoci metabolismus   patofyziologie   MeSH
• proteiny SNARE metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• proteiny SNARE MeSH

Vesicles mediate the trafficking of membranes/proteins in the endocytic and secretory pathways. These pathways are regulated by small GTPases of the Rab family. Rab proteins belong to the Ras superfamily of GTPases, which are significantly involved in various intracellular trafficking and signaling processes in the nervous system. Rab11 is known to play a key role especially in recycling many proteins, including receptors important for signal transduction and preservation of functional activities of nerve cells. Rab11 activity is controlled by GEFs (guanine exchange factors) and GAPs (GTPase activating proteins), which regulate its function through modulating GTP/GDP exchange and the intrinsic GTPase activity, respectively. Rab11 is involved in the transport of several growth factor molecules important for the development and repair of neurons. Overexpression of Rab11 has been shown to significantly enhance vesicle trafficking. On the other hand, a reduced expression of Rab11 was observed in several neurodegenerative diseases. Current evidence appears to support the notion that Rab11 and its cognate proteins may be potential targets for therapeutic intervention. In this review, we briefly discuss the function of Rab11 and its related interaction partners in intracellular pathways that may be involved in neurodegenerative processes.

• Klíčová slova
• Rab11, Rab11-FIPs, neurodegenerative diseases, vesicle trafficking,
• MeSH
• biologický transport genetika   fyziologie   MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• neurodegenerativní nemoci * genetika   metabolismus   MeSH
• neurony metabolismus   MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• membránové proteiny MeSH
• rab11 protein MeSH Prohlížeč

Transcranial sonography is a highly sensitive noninvasive sonographic method for detection of early and specific echogenic changes in basal ganglia of patients with some neurodegenerative diseases. Transcranial sonography showed substantia nigra hyperechogenicity as a typical echo feature in idiopathic Parkinson disease and lenticular nucleus hyperechogenicity as a characteristic finding in atypical parkinsonian syndromes. Brain stem raphe hypoechogenicity or interruption has been shown to be highly prevalent in patients with unipolar depression as well as depression associated with certain neurodegenerative diseases. Transcranial sonography also revealed basal ganglia hyperechoic changes in movement disorders with trace metal accumulation such as Wilson disease, some entities of neurodegeneration with brain iron accumulation, as well as several forms of spinocerebellar ataxia. Transcranial sonography is a valuable neuro imaging method for early and differential diagnosis and follow-up of patients with neurodegenerative and psychiatric diseases.

• Klíčová slova
• basal ganglia echogenicity, neurodegenerative diseases, psychiatric diseases, transcranial sonography, ultrasound education,
• MeSH
• duševní poruchy diagnostické zobrazování   MeSH
• lidé MeSH
• neurodegenerativní nemoci diagnostické zobrazování   MeSH
• ultrasonografie dopplerovská transkraniální metody   MeSH
• vylepšení obrazu metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The term neurodegenerative diseases include a long list of diseases affecting the nervous system that are characterized by the degeneration of different neurological structures. Among them, Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) are the most representative ones. The vast majority of cases are sporadic and results from the interaction of genes and environmental factors in genetically predisposed individuals. Among environmental conditions, electromagnetic field exposure has begun to be assessed as a potential risk factor for neurodegeneration. In this review, we discuss the existing literature regarding electromagnetic fields and neurodegenerative diseases. Epidemiological studies in AD, PD, and ALS have shown discordant results; thus, a clear correlation between electromagnetic exposure and neurodegeneration has not been demonstrated. In addition, we discuss the role of electromagnetic radiation as a potential non-invasive therapeutic strategy for some neurodegenerative diseases, particularly for PD and AD.

• Klíčová slova
• Alzheimer’s disease, Amyotrophic lateral sclerosis, Electromagnetic fields, Neurodegenerative diseases, Parkinson’s disease,
• MeSH
• Alzheimerova nemoc * epidemiologie   MeSH
• amyotrofická laterální skleróza * epidemiologie   MeSH
• elektromagnetická pole MeSH
• lidé MeSH
• neurodegenerativní nemoci * epidemiologie   MeSH
• Parkinsonova nemoc * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Disturbance of cerebral iron regulation is almost universal in neurodegenerative disorders. There is a growing body of evidence that increased iron deposits may contribute to degenerative changes. Thus, the effect of iron chelation therapy has been investigated in many neurological disorders including rare genetic syndromes with neurodegeneration with brain iron accumulation as well as common sporadic disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review summarizes recent advances in understanding the role of iron in the etiology of neurodegeneration. Outcomes of studies investigating the effect of iron chelation therapy in neurodegenerative disorders are systematically presented in tables. Iron chelators, particularly the blood brain barrier-crossing compound deferiprone, are capable of decreasing cerebral iron in areas with abnormally high concentrations as documented by MRI. Yet, currently, there is no compelling evidence of the clinical effect of iron removal therapy on any neurological disorder. However, several studies indicate that it may prevent or slow down disease progression of several disorders such as aceruloplasminemia, pantothenate kinase-associated neurodegeneration or Parkinson's disease.

• Klíčová slova
• Friedreich’s ataxia, Iron chelation, Multiple sclerosis, NBIA, Parkinson’s disease, Superficial siderosis,
• MeSH
• chelátory železa terapeutické užití   MeSH
• lidé MeSH
• neurodegenerativní nemoci farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• chelátory železa MeSH

Neurodegenerative disease (ND) incidence has recently increased due to improved life expectancy. Alzheimer's (AD) or Parkinson's disease (PD) are the most prevalent NDs. Both diseases are poly genetic, multifactorial and heterogenous. Preventive medicine, a healthy diet, exercise, and controlling comorbidities may delay the onset. After the diseases are diagnosed, therapy is needed to slow progression. Recent studies show that local, peripheral and age-related inflammation accelerates NDs' onset and progression. Patients with autoimmune disorders like inflammatory bowel disease (IBD) could be at higher risk of developing AD or PD. However, no increase in ND incidence has been reported if the patients are adequately diagnosed and treated. Autoantibodies against abnormal tau, β amyloid and α- synuclein have been encountered in AD and PD and may be protective. This discovery led to the proposal of immune-based therapies for AD and PD involving monoclonal antibodies, immunization/ vaccines, pro-inflammatory cytokine inhibition and anti-inflammatory cytokine addition. All the different approaches have been analysed here. Future perspectives on new therapeutic strategies for both disorders are concisely examined.

• Klíčová slova
• Alzheimer's disease (AD), Neurodegenerative diseases (NDs), Parkinson's disease (PD), autoimmunity, neurodegeneration, neuroinflammation, tau, therapy, vaccines., α-synuclein, β-amyloid,
• MeSH
• alfa-synuklein MeSH
• Alzheimerova nemoc * farmakoterapie   MeSH
• autoimunita MeSH
• autoimunitní nemoci * MeSH
• cytokiny MeSH
• lidé MeSH
• neurodegenerativní nemoci * terapie   MeSH
• Parkinsonova nemoc * farmakoterapie   MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa-synuklein MeSH
• cytokiny MeSH

The worldwide increase in the incidence of obesity and cardiovascular and neurodegenerative diseases, e.g. Alzheimer's disease, is related to many factors, including an unhealthy lifestyle and aging populations. However, the interconnection between these diseases is not entirely clear, and it is unknown whether common mechanisms underlie these conditions. Moreover, there are currently no fully effective therapies for obesity and neurodegeneration. While there has been extensive research in preclinical models addressing these issues, the experimental findings have not been translated to the clinic. Another challenge relates to the time of onset of individual diseases, which may not be easily identified, since there are no specific indicators or biomarkers that define disease onset. Hence knowing when to commence preventive treatment is unclear. This is especially pertinent in neurodegenerative diseases, where the onset of the disease may be subtle and occur decades before the signs and symptoms manifest. In metabolic and cardiovascular disorders, the risk may occur in-utero, in line with the concept of fetal programming. This review provides a brief overview of the link between obesity, cardiovascular and neurodegenerative diseases and discusses potential common mechanisms including the role of the gut microbiome.

• MeSH
• Alzheimerova nemoc * metabolismus   MeSH
• lidé MeSH
• neurodegenerativní nemoci * metabolismus   MeSH
• obezita komplikace   diagnóza   epidemiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The exact signaling leading to neurological dysfunction in neurodegenerative diseases is currently unknown. We hypothesize that the c-Jun N-terminal kinase (JNK) signaling pathway is a potential therapeutic target for neurodegenerative diseases. This postulate rests on extensive data from cell and animal experimental studies, demonstrating that JNK signaling plays a crucial role in the pathogenesis of neurodegenerative diseases. The sustained activation of JNK leads to synaptic dysfunction and even neuronal apoptosis, ultimately resulting in memory deficits and neurodegeneration. JNK phosphorylates the amyloid precursor protein and tau, ultimately resulting in the formation of extraneuronal senile plaques and intraneuronal neurofibrillary tangles. Our hypothesis could be validated by investigating the cerebral cortex of elderly chimpanzees injected with phosphorylated JNK or transgenic pig and chimpanzee models established using gene editing technology including CRISPR. This hypothesis provides clues for further understanding the molecular mechanisms of neurodegenerative diseases and the development of potential target therapeutic drugs.

• Klíčová slova
• Alzheimer's disease, JNK, amyloid beta, neurodegenerative diseases, tau,
• MeSH
• Alzheimerova nemoc genetika   MeSH
• amyloidní beta-protein * metabolismus   MeSH
• amyloidový prekurzorový protein beta * genetika   metabolismus   MeSH
• fosforylace MeSH
• genový targeting * MeSH
• JNK mitogenem aktivované proteinkinasy metabolismus   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• mozková kůra metabolismus   patologie   MeSH
• neurodegenerativní nemoci patologie   MeSH
• neurony metabolismus   MeSH
• Pan troglodytes MeSH
• prasata MeSH
• proteiny tau metabolismus   MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• amyloidní beta-protein * MeSH
• amyloidový prekurzorový protein beta * MeSH
• JNK mitogenem aktivované proteinkinasy MeSH
• proteiny tau MeSH

BACKGROUND: Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy. CONCLUSION: Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.

• Klíčová slova
• Neurodegenerative diseases, blood-brain barrier, dietary adaptations., gut microbiota, microbiota-gut-brain axis, therapy,
• MeSH
• dysbióza metabolismus   MeSH
• hematoencefalická bariéra metabolismus   MeSH
• lidé MeSH
• mozek * metabolismus   MeSH
• neurodegenerativní nemoci * mikrobiologie   metabolismus   MeSH
• osa mozek-střevo * fyziologie   MeSH
• probiotika MeSH
• stárnutí * MeSH
• střevní mikroflóra * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Increasing evidence has revealed that cellular senescence drives NDs, including Alzheimer's disease (AD) and Parkinson's disease. Different senescent cell populations secrete senescence-associated secretory phenotypes (SASP), including matrix metalloproteinase-3, interleukin (IL)-1α, IL-6, and IL-8, which can harm adjacent microglia. Moreover, these cells possess high expression levels of senescence hallmarks (p16 and p21) and elevated senescence-associated β-galactosidase activity in in vitro and in vivo ND models. These senescence phenotypes contribute to the deposition of β-amyloid and tau-protein tangles. Selective clearance of senescent cells and SASP regulation by inhibiting p38/mitogen-activated protein kinase and nuclear factor kappa B signaling attenuate β-amyloid load and prevent tau-protein tangle deposition, thereby improving cognitive performance in AD mouse models. In addition, telomere shortening, a cellular senescence biomarker, is associated with increased ND risks. Telomere dysfunction causes cellular senescence, stimulating IL-6, tumor necrosis factor-α, and IL-1β secretions. The forced expression of telomerase activators prevents cellular senescence, yielding considerable neuroprotective effects. This review elucidates the mechanism of cellular senescence in ND pathogenesis, suggesting strategies to eliminate or restore senescent cells to a normal phenotype for treating such diseases.

• Klíčová slova
• Alzheimer’s disease, Amyloid β · tau protein, Cellular senescence, Neurodegenerative diseases, Telomere shortening,
• MeSH
• Alzheimerova nemoc MeSH
• amyloidní beta-protein metabolismus   MeSH
• lidé MeSH
• neurodegenerativní nemoci * MeSH
• Parkinsonova nemoc metabolismus   MeSH
• sekreční fenotyp asociovaný se senescencí MeSH
• signální transdukce MeSH
• stárnutí buněk * účinky léků   MeSH
• zkracování telomer účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• amyloidní beta-protein MeSH