Movement disorders : official journal of the Movement Disorder Society · 2025
Cerebrospinal Fluid Biomarkers of NLRP3 Pathway, Immune Dysregulation, and Neurodegeneration in Parkinson's Disease: A Meta-Analysis.
СтатьяМетаанализНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Marinescu Alina-Măriuca, Machado Venissa, Pagano Gennaro, Muelhardt Nicoletta Milani, Kustermann Thomas, Mracsko Eva Zsuzsanna, Brockmann Kathrin, Shariati Nima, Anzures-Cabrera Judith, Zinnhardt Bastian
Аннотация
BACKGROUND: The activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and associated immune dysregulation is one of the key pathological processes preceding and accompanying α-synuclein pathology, neuronal damage, and cell death in Parkinson's disease (PD). Biomarkers indicative of ongoing immune dysregulation could potentially serve as early indicators of disease activity and may support the development of novel immunomodulatory therapies.
METHODS: We performed a meta-analysis on 17 biomarkers related to specific components of the neuroinflammatory response in the cerebrospinal fluid of people with PD (PwP) and controls. We included studies that measured biomarkers related to NLRP3 inflammasome priming and activation (interleukin [IL]-1β, IL-18, IL-6, C-reactive protein, tumor necrosis factor [TNF]-α); reactive glial cells (soluble triggering receptor expressed on myeloid cells 2, chitinase 3-like-protein 1, glial fibrillary acidic protein, and s100); neurodegeneration (neurofilament light chain [NfL]); and other inflammatory mediators (interferon-ɣ, IL-2, IL-4, IL-8, IL-10, monocyte chemoattractant protein-1, chemokine C-X3-C motif chemokine ligand 1).
RESULTS: Random-effects meta-analyses show markers downstream of the NLRP3 inflammasome priming and activation (IL-1β, IL-6, TNF-α), the astrocytic marker s100 calcium-binding protein B and neuroaxonal damage marker NfL are significantly increased in the cerebrospinal fluid (CSF) of PwP.
CONCLUSIONS: The elevation in key downstream and general inflammatory mediators results is consistent with the hypothesized involvement of the NLRP3 inflammasome pathway and neurodegeneration in PD pathogenesis. These results highlight the potential use of CSF inflammatory markers and support further investigation into immunomodulatory strategies for PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
METHODS: We performed a meta-analysis on 17 biomarkers related to specific components of the neuroinflammatory response in the cerebrospinal fluid of people with PD (PwP) and controls. We included studies that measured biomarkers related to NLRP3 inflammasome priming and activation (interleukin [IL]-1β, IL-18, IL-6, C-reactive protein, tumor necrosis factor [TNF]-α); reactive glial cells (soluble triggering receptor expressed on myeloid cells 2, chitinase 3-like-protein 1, glial fibrillary acidic protein, and s100); neurodegeneration (neurofilament light chain [NfL]); and other inflammatory mediators (interferon-ɣ, IL-2, IL-4, IL-8, IL-10, monocyte chemoattractant protein-1, chemokine C-X3-C motif chemokine ligand 1).
RESULTS: Random-effects meta-analyses show markers downstream of the NLRP3 inflammasome priming and activation (IL-1β, IL-6, TNF-α), the astrocytic marker s100 calcium-binding protein B and neuroaxonal damage marker NfL are significantly increased in the cerebrospinal fluid (CSF) of PwP.
CONCLUSIONS: The elevation in key downstream and general inflammatory mediators results is consistent with the hypothesized involvement of the NLRP3 inflammasome pathway and neurodegeneration in PD pathogenesis. These results highlight the potential use of CSF inflammatory markers and support further investigation into immunomodulatory strategies for PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.