Molecular Neurobiology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 31, 2025
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)
Опубликована: Июль 12, 2023
Abstract Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s so on, have suggested that inflammation is not only a result of neurodegeneration but also crucial player this process. Protein aggregates which are very common pathological phenomenon can induce neuroinflammation further aggravates protein aggregation neurodegeneration. Actually, even happens earlier than aggregation. Neuroinflammation induced by genetic variations CNS cells or peripheral immune may deposition some susceptible population. Numerous signaling pathways range been to be involved the pathogenesis neurodegeneration, although they still far from being completely understood. Due limited success traditional treatment methods, blocking enhancing inflammatory considered promising strategies for therapy many them got exciting results animal models clinical trials. Some them, few, approved FDA usage. Here we comprehensively review factors affecting major pathogenicity sclerosis. We summarize current strategies, both clinic, diseases.
Язык: Английский
Процитировано
587
Journal of Neural Transmission, Год журнала: 2023, Номер 130(6), С. 827 - 838
Опубликована: Май 11, 2023
The heterogeneity of Parkinson's disease (PD), i.e. the various clinical phenotypes, pathological findings, genetic predispositions and probably also implicated pathophysiological pathways pose a major challenge for future research projects therapeutic trail design. We outline several concepts, mechanisms, including presumed roles α-synuclein misfolding aggregation, Lewy bodies, oxidative stress, iron melanin, deficient autophagy processes, insulin incretin signaling, T-cell autoimmunity, gut-brain axis evidence that microbial (viral) agents may induce molecular hallmarks neurodegeneration. hypothesis is discussed, whether PD might indeed be triggered by exogenous (infectious) in susceptible individuals upon entry via olfactory bulb (brain first) or gut (body-first), which would support idea mechanisms change over time. unresolved have contributed to failure past trials, attempted slow course PD. thus conclude patients need personalized approaches tailored specific phenomenological etiologic subtypes disease.
Язык: Английский
Процитировано
70
Journal of Neuroscience Research, Год журнала: 2023, Номер 101(6), С. 952 - 975
Опубликована: Янв. 30, 2023
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in substantia nigra. The hallmarks are presence Lewy bodies composed mainly aggregated α-synuclein and immune activation inflammation brain. neurotropism SARS-CoV-2 with induction cytokine storm neuroinflammation can contribute to development PD. Interestingly, overexpression PD patients may limit neuroinvasion degeneration neurons; however, on other hand, this virus speed up aggregation. review aims discuss potential link between COVID-19 risk PD, highlighting need for further studies authenticate association. We have also overviewed influence infection course management. In context, we presented prospects controlling pandemic related cases that, beyond global vaccination novel anti-SARS-CoV-2 agents, include graphene-based nanoscale platforms offering antiviral anti-amyloid strategies against
Язык: Английский
Процитировано
37
Nature Neuroscience, Год журнала: 2024, Номер unknown
Опубликована: Окт. 8, 2024
Язык: Английский
Процитировано
14
Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102540 - 102540
Опубликована: Окт. 10, 2024
Язык: Английский
Процитировано
14
Neurology, Год журнала: 2025, Номер 104(3)
Опубликована: Янв. 13, 2025
Lewy body diseases (LBDs) such as Parkinson disease (PD) feature increased deposition of α-synuclein (α-syn) in cutaneous sympathetic noradrenergic nerves. The pathophysiologic significance intraneuronal α-syn is unclear. We reviewed data about immunoreactive α-syn, tyrosine hydroxylase (TH, a marker catecholaminergic fibers), and the neurotransmitter norepinephrine (NE) skin biopsies from control participants patients with PD, related LBD pure autonomic failure (PAF), non-LBD synucleinopathy multiple system atrophy (MSA), or neurologic postacute sequelae severe acute respiratory syndrome coronavirus 2 (neuro-PASC). In retrospective observational study, we α-syn-TH colocalization indexes TH signal intensities arrector pili muscles, blood vessels, sweat glands neck NE concentrations simultaneously obtained thigh studied at NIH Clinical Center. LBD, MSA, group were assessed by analyses variance Tukey post hoc test for comparisons. Similar performed PD neuro-PASC vs control. Dermal examined 18 controls (mean age 58 years, 50% female) 53 (66, 34%), 15 MSA (61, 33%), 11 (52, 82%) patients. had higher than difference = 1.495, 95% CI 1.081-1.909, p < 0.0001) all 3 constituents (arrector pili: mean 2.743, 1.608-3.879, 0.0001; vessels: 2.157, 1.095-3.219, glands: 4.136, 1.704-6.567, 0.0001). groups did not differ either NE. elevated compared controls, also no differences contents. LBDs entail biopsies, without evidence local denervation deficiency. results fail to support toxicity nerves neuro-PASC. raise possibility part postinfectious immune inflammatory processes.
Язык: Английский
Процитировано
2
Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Янв. 18, 2025
HIV-associated neurocognitive disorders (HAND) and viral reservoirs in the brain remain a significant challenge. Despite their importance, mechanisms allowing HIV-1 entry replication central nervous system (CNS) are poorly understood. Here, we show that α-synuclein (to lesser extent) Aβ fibrils associated with neurological diseases enhance human T cells, macrophages, microglia. Additionally, an Env-derived amyloidogenic peptide accelerated amyloid formation by peptides. Mechanistic studies interact particles promote virion attachment fusion target cells. overall negative surface charge, these facilitate interactions between cellular membranes. The enhancing effects of extracts on infection correlated binding to Thioflavin T, dye commonly used stain amyloids. Our results suggest detrimental interplay amyloids may contribute development neurodegenerative diseases.
Язык: Английский
Процитировано
2
Journal of Neurology, Год журнала: 2022, Номер 270(3), С. 1346 - 1360
Опубликована: Дек. 3, 2022
Abstract Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder characterized by motor and non-motor disturbances as result of complex not fully understood pathogenesis, probably including neuroinflammation, oxidative stress, formation alpha-synuclein (α-syn) aggregates. As age the main risk factor for several disorders PD, aging immune system leading to inflammaging immunosenescence may contribute neuroinflammation PD onset progression; abnormal α-syn aggregation in context dysfunction favor activation nucleotide-binding oligomerization domain-like receptor (NOD) family pyrin domain containing 3 (NLRP3) inflammasome within microglial cells through interaction with toll-like receptors (TLRs). This process would further lead Caspase (Cas)-1, increased production pro-inflammatory cytokines (PC), subsequent impairment mitochondria damage dopaminergic neurons. All these phenomena are mediated translocation nuclear kappa-B (NF-κB) enhanced reactive oxygen species (ROS). To date, drugs treat mainly aimed at relieving clinical symptoms there no disease-modifying options reverse or stop progression. review outlines role TLR/NLRP3/Cas-1 pathway PD-related dysfunction, also focusing on specific therapeutic that might be used since early stages counteract dysfunction.
Язык: Английский
Процитировано
34
Revue Neurologique, Год журнала: 2023, Номер 179(9), С. 937 - 946
Опубликована: Март 16, 2023
The suspicion of an origin Parkinson's disease (PD) at the periphery body and involvement environmental risk factors in pathogenesis PD have directed attention scientific community towards microbiota. microbiota represents all microorganisms residing both on a host. It plays essential role physiological functioning In this article, we review dysbiosis repeatedly demonstrated how it influences symptoms. Dysbiosis is associated with motor non-motor animal models, only promotes symptoms individuals genetically susceptible to disease, suggesting that factor but not cause disease. We also contributes pathophysiology PD. induces numerous complex metabolic changes, resulting increased intestinal permeability, local systemic inflammation, production bacterial amyloid proteins promote α-synuclein aggregation, as well decrease short-chain fatty acid-producing bacteria anti-inflammatory neuroprotective potential. addition, decreases efficacy dopaminergic treatments. then discuss interest analysis biomarker Finally, give overview interventions modulating gut such dietary interventions, pro-biotics, decontamination fecal transplantation could influence course
Язык: Английский
Процитировано
23
Biomolecules, Год журнала: 2023, Номер 13(5), С. 865 - 865
Опубликована: Май 19, 2023
The etiology of Parkinson’s disease (PD) is poorly understood, and strongly suspected to include both genetic environmental factors. In this context, it essential investigate possible biomarkers for prognostic diagnostic purposes. Several studies reported dysregulated microRNA expression in neurodegenerative disorders, including PD. Using ddPCR, we investigated the concentrations miR-7-1-5p, miR-499-3p, miR-223-3p miR-223-5p—miRNAs involved α-synuclein pathway inflammation—in serum serum-isolated exosomes 45 PD patients 49 age- sex-matched healthy controls (HC). While miR-499-3p miR-223-5p showed no differences (1), concentration miR-7-1-5p was significantly increased (p = 0.0007 vs. HC) (2) 0.0006) exosome 0.0002) were increased. ROC curve analysis that discriminates between HC 0.0001, cases). Notably, patients, 0.0008) 0.006) correlated with levodopa equivalent daily dosage (LEDD). Finally, compared 0.025), 0.05). Our results suggest miR-223-3p, distinguishing from HC, have potential be useful non-invasive disease.
Язык: Английский
Процитировано
23