Role of neuroinflammation in neurodegeneration development

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 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.

Language: Английский

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The heterogeneity of Parkinson’s disease

Journal of Neural Transmission, Journal Year: 2023, Volume and Issue: 130(6), P. 827 - 838

Published: May 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.

Language: Английский

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α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 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.

Language: Английский

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SARS‐COV‐2 infection and Parkinson's disease: Possible links and perspectives

Journal of Neuroscience Research, Journal Year: 2023, Volume and Issue: 101(6), P. 952 - 975

Published: Jan. 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

Language: Английский

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Immunosenescence and Inflammaging: Mechanisms and Role in Diseases

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102540 - 102540

Published: Oct. 10, 2024

Language: Английский

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Modeling Parkinson’s disease pathology in human dopaminergic neurons by sequential exposure to α-synuclein fibrils and proinflammatory cytokines

Nature Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 8, 2024

Language: Английский

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Research Priorities on the Role of α‐Synuclein in Parkinson's Disease Pathogenesis

Movement Disorders, Journal Year: 2024, Volume and Issue: 39(10), P. 1663 - 1678

Published: June 30, 2024

Abstract Various forms of Parkinson's disease, including its common sporadic form, are characterized by prominent α‐synuclein (αSyn) aggregation in affected brain regions. However, the role αSyn pathogenesis and evolution disease remains unclear, despite vast research efforts more than a quarter century. A better understanding αSyn, either primary or secondary, is critical for developing disease‐modifying therapies. Previous attempts to hone this have been challenged experimental limitations, but recent technological advances may facilitate progress. The Scientific Issues Committee International Parkinson Movement Disorder Society (MDS) charged panel experts field discuss current scientific priorities identify strategies with potential breakthrough. © 2024 Author(s). Disorders published Wiley Periodicals LLC on behalf Society.

Language: Английский

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Pathophysiological Significance of α-Synuclein in Sympathetic Nerves

Neurology, Journal Year: 2025, Volume and Issue: 104(3)

Published: Jan. 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.

Language: Английский

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Toll-like receptors and NLRP3 inflammasome-dependent pathways in Parkinson’s disease: mechanisms and therapeutic implications

Journal of Neurology, Journal Year: 2022, Volume and Issue: 270(3), P. 1346 - 1360

Published: Dec. 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.

Language: Английский

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Serum and Exosomal miR-7-1-5p and miR-223-3p as Possible Biomarkers for Parkinson’s Disease

Biomolecules, Journal Year: 2023, Volume and Issue: 13(5), P. 865 - 865

Published: May 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.

Language: Английский

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