Role of Specific Autoantibodies in Neurodegenerative Diseases: Pathogenic Antibodies or Promising Biomarkers for Diagnosis DOI Creative Commons
Dimitrina Miteva, Georgi Vasilev, Tsvetelina Velikova

и другие.

Antibodies, Год журнала: 2023, Номер 12(4), С. 81 - 81

Опубликована: Дек. 8, 2023

Neurodegenerative diseases (NDDs) affect millions of people worldwide. They develop due to the pathological accumulation and aggregation various misfolded proteins, axonal synaptic loss dysfunction, inflammation, cytoskeletal abnormalities, defects in DNA RNA, neuronal death. This leads activation immune responses release antibodies against them. Recently, it has become clear that autoantibodies (Aabs) can contribute demyelination, loss, brain cognitive dysfunction. significantly changed understanding participation humoral autoimmunity neurodegenerative disorders. It is crucial understand how neuroinflammation involved neurodegeneration, aid improving diagnostic therapeutic value Aabs future. review aims provide data on system's role NDDs, pathogenic some specific molecules associated with most common their potential as biomarkers for monitoring diagnosing NDDs. suggested autoimmune aspects NDDs will facilitate early diagnosis help elucidate previously unknown pathobiology these diseases.

Язык: Английский

α-Synuclein in synaptic function and dysfunction DOI Creative Commons
Manu Sharma, Jacqueline Burré

Trends in Neurosciences, Год журнала: 2022, Номер 46(2), С. 153 - 166

Опубликована: Дек. 23, 2022

Язык: Английский

Процитировано

107
Advances in understanding the function of alpha-synuclein: implications for Parkinson’s disease DOI Creative Commons
Paolo Calabresi, Giulia Di Lazzaro, Gioia Marino

и другие.

Brain, Год журнала: 2023, Номер 146(9), С. 3587 - 3597

Опубликована: Май 15, 2023

The critical role of alpha-synuclein in Parkinson's disease represents a pivotal discovery. Some progress has been made over recent years identifying disease-modifying therapies for that target alpha-synuclein. However, these treatments have not yet shown clear efficacy slowing the progression this disease. Several explanations exist issue. pathogenesis is complex and fully clarified heterogeneity disease, with diverse genetic susceptibility risk factors different clinical courses, adds further complexity. Thus, deep understanding physiological pathophysiological functions crucial. In review, we first describe cellular animal models developed to study pathological roles protein, including transgenic techniques, use viral vectors intracerebral injections fibrils. We then provide evidence tools are crucial modelling pathogenesis, causing protein misfolding aggregation, synaptic dysfunction, brain plasticity impairment cell-to-cell spreading species. particular, focus on possibility dissecting pre- postsynaptic effects both conditions. Finally, show how vulnerability specific neuronal cell types may facilitate systemic dysfunctions leading multiple network alterations. These functional alterations underlie motor non-motor manifestations occur before overt neurodegeneration. now understand therapeutic targeting patients requires caution, since exerts important functions. Moreover, interactions other molecules induce synergistic detrimental effects. only might be enough. Combined should considered future.

Язык: Английский

Процитировано

65
Alpha Synuclein: Neurodegeneration and Inflammation DOI Open Access
Gianluigi Forloni

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5914 - 5914

Опубликована: Март 21, 2023

Alpha-Synuclein (α-Syn) is one of the most important molecules involved in pathogenesis Parkinson’s disease and related disorders, synucleinopathies, but also several other neurodegenerative disorders with a more elusive role. This review analyzes activities α-Syn, different conformational states, monomeric, oligomeric fibrils, relation to neuronal dysfunction. The damage induced by α-Syn various conformers will be analyzed its capacity spread intracellular aggregation seeds prion-like mechanism. In view prominent role inflammation virtually all activity illustrated considering influence on glial reactivity. We others have described interaction between general cerebral dysfunctional α-Syn. Differences microglia astrocyte activation been observed when vivo presence oligomers has combined lasting peripheral inflammatory effect. reactivity was amplified, while astrocytes were damaged double stimulus, opening new perspectives for control synucleinopathies. Starting from our studies experimental models, we extended perspective find useful pointers orient future research potential therapeutic strategies disorders.

Язык: Английский

Процитировано

61
Cell biology of Parkinson's disease: Mechanisms of synaptic, lysosomal, and mitochondrial dysfunction DOI
Sarah M. Brooker, G Naylor, Dimitri Krainc

и другие.

Current Opinion in Neurobiology, Год журнала: 2024, Номер 85, С. 102841 - 102841

Опубликована: Фев. 1, 2024

Язык: Английский

Процитировано

26
Conformationally adaptive therapeutic peptides for diseases caused by intrinsically disordered proteins (IDPs). New paradigm for drug discovery: Target the target, not the arrow DOI Creative Commons
Jacques Fantini, Fodil Azzaz, Coralie Di Scala

и другие.

Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown, С. 108797 - 108797

Опубликована: Янв. 1, 2025

The traditional model of protein structure determined by the amino acid sequence is today seriously challenged fact that approximately half human proteome made up proteins do not have a stable 3D structure, either partially or in totality. These proteins, called intrinsically disordered (IDPs), are involved numerous physiological functions and associated with severe pathologies, e.g. Alzheimer, Parkinson, Creutzfeldt-Jakob, amyotrophic lateral sclerosis (ALS), type 2 diabetes. Targeting these challenging for two reasons: i) we need to preserve their functions, ii) drug design molecular docking possible due lack reliable starting conditions. Faced this challenge, solutions proposed artificial intelligence (AI) such as AlphaFold clearly unsuitable. Instead, suggest an innovative approach consisting mimicking, short synthetic peptides, conformational flexibility IDPs. which call adaptive derived from domains IDPs become structured after interacting ligand. Adaptive peptides designed aim selectively antagonizing harmful effects IDPs, without targeting them directly but through selected ligands, affecting properties. This"target target, arrow" strategy promised open new route discovery currently undruggable proteins.

Язык: Английский

Процитировано

4
The Interplay between α-Synuclein and Microglia in α-Synucleinopathies DOI Open Access
Jacob Deyell, Manjari Sriparna, Mingyao Ying

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2477 - 2477

Опубликована: Янв. 27, 2023

Synucleinopathies are a set of devastating neurodegenerative diseases that share pathologic accumulation the protein α-synuclein (α-syn). This causes neuronal death resulting in irreversible dementia, deteriorating motor symptoms, and cognitive decline. While etiology these conditions remains largely unknown, microglia, resident immune cells central nervous system (CNS), have been consistently implicated pathogenesis synucleinopathies. Microglia generally believed to be neuroprotective early stages α-syn contribute further neurodegeneration chronic disease states. molecular mechanisms by which microglia achieve this role still being investigated, here we highlight major findings date. In review, describe how structural varieties inherently disordered result varied microglial receptor-mediated interactions. We also summarize receptors enable cellular recognition uptake α-syn. Lastly, review downstream effects processing within including spread other brain regions neuroinflammation Understanding mechanism interactions with is vital conceptualizing targets for novel therapeutic interventions. addition, given significant diversity pathophysiology synucleinopathies, such gauging all potential pathways state.

Язык: Английский

Процитировано

33
Application of Nanobiosensor Engineering in the Diagnosis of Neurodegenerative Disorders DOI Creative Commons

Thikra S. Dhahi,

Alaa Kamal Yousif Dafhalla, A. Wesam Al-Mufti

и другие.

Results in Engineering, Год журнала: 2024, Номер 24, С. 102790 - 102790

Опубликована: Сен. 5, 2024

Язык: Английский

Процитировано

11
The roles of intrinsically disordered proteins in neurodegeneration DOI Creative Commons
Kagistia Hana Utami, Satoru Morimoto, Yasue Mitsukura

и другие.

Biochimica et Biophysica Acta (BBA) - General Subjects, Год журнала: 2025, Номер unknown, С. 130772 - 130772

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

2
α-synuclein and tau: interactions, cross-seeding, and the redefinition of synucleinopathies as complex proteinopathies DOI Creative Commons
Francisco J. Padilla-Godínez,

Eunice Ruth Vázquez-García,

María Isabel Trujillo-Villagrán

и другие.

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Март 27, 2025

Neurodegenerative diseases are characterized by protein aggregation and overlapping pathologies, challenging traditional classifications highlighting shared underlying mechanisms. Parkinson’s disease related synucleinopathies, including Lewy body dementia multiple system atrophy, highlight the interplay between α-synuclein tau, two key proteins implicated in these disorders. Recent studies reveal that tau co-aggregate, interact synergistically, propagate via prion-like mechanisms, exacerbating neuronal dysfunction. This review examines physiological roles pathological transitions of α-synuclein, emphasizing their microtubule dynamics, synaptic regulation, structural heterogeneity aggregates. Evidence from post-mortem brains, transgenic models, proteomic analyses underscores significance soluble oligomers as primary neurotoxic species explores diverse molecular composition bodies glial cytoplasmic inclusions. The co-localization influenced genetic factors post-translational modifications, offers insights into mechanisms across synucleinopathies tauopathies. These findings advocate for integrated therapeutic strategies targeting cross-seeding proteostatic disruption while preserving roles. By framing neurodegeneration a collapse networks rather than isolated proteinopathies, this work proposes paradigm shift toward understanding treating complex neurodegenerative

Язык: Английский

Процитировано

2
A personalised and comprehensive approach is required to suppress or replenish SNCA for Parkinson’s disease DOI Creative Commons
Dunhui Li, Wai Yan Yau,

Shengdi Chen

и другие.

npj Parkinson s Disease, Год журнала: 2025, Номер 11(1)

Опубликована: Март 4, 2025

Based on the prevailing α-synuclein "gain-of-function" hypothesis, reducing levels and removing its aggregates is a current focus of disease-modifying therapies for Parkinson's disease. Emerging evidence "loss-of-function" suggests that it may be necessary to replenish monomeric levels. We propose personalized comprehensive approach different subgroups based whether likely contribute disease pathogenesis through "gain-of-function", "loss-of-function", or both mechanisms.

Язык: Английский

Процитировано

1