Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson’s disease DOI Creative Commons
Sara A. Ferreira, Conghui Li, Ida Hyllen Klæstrup

и другие.

npj Parkinson s Disease, Год журнала: 2023, Номер 9(1)

Опубликована: Дек. 13, 2023

Alpha-synuclein (α-syn) aggregation and immune activation represent hallmark pathological events in Parkinson's disease (PD). The PD-associated response encompasses both brain peripheral cells, although little is known about the proteins relevant for such a response. We propose that upregulation of CD163 observed blood monocytes responsive microglia PD patients protective mechanism disease. To investigate this, we used model based on intrastriatal injections murine α-syn pre-formed fibrils knockout (KO) mice wild-type littermates. CD163KO females revealed an impaired differential early to pathology as by immunohistochemical transcriptomic analysis. After 6 months, showed exacerbated pathology, which ultimately led dopaminergic neurodegeneration greater magnitude. These findings support sex-dimorphic neuroprotective role during α-syn-induced neurodegeneration.

Язык: Английский

Dopaminergic regulation of inflammation and immunity in Parkinson's disease: friend or foe? DOI Creative Commons
Alessia Furgiuele, Frederico C. Pereira, Stefano De Martini

и другие.

Clinical & Translational Immunology, Год журнала: 2023, Номер 12(10)

Опубликована: Янв. 1, 2023

Abstract Parkinson's disease (PD) is a neurodegenerative affecting 7–10 million people worldwide. Currently, there no treatment available to prevent or delay PD progression, partially due the limited understanding of pathological events which lead death dopaminergic neurons in substantia nigra brain, known be cause symptoms. The current treatments aim at compensating dopamine (DA) deficiency brain using its precursor levodopa, agonists and some indirect agents. immune system emerging as critical player PD. Therefore, immune‐based approaches have recently been proposed used potential antiparkinsonian It has well‐known that pathways play significant role regulating responses brain. Although agents are primary treatments, their regulatory effect yet fully understood. present review summarises evidence effects DA mimics discusses drugs. Based on involvement regulation neuroinflammation PD, we propose targeting involved pathology could offer better outcome for patients.

Язык: Английский

Процитировано

11
The Role of Immune Dysfunction in Parkinson’s Disease Development DOI Open Access
Davide Cossu, Taku Hatano, Nobutaka Hattori

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(23), С. 16766 - 16766

Опубликована: Ноя. 26, 2023

Recent research has unveiled intriguing insights suggesting that the body’s immune system may be implicated in Parkinson’s disease (PD) development. Studies have observed disparities pro-inflammatory and anti-inflammatory markers between PD patients healthy individuals. This finding underscores potential influence of dysfunction genesis this condition. A dysfunctional can serve as a primary catalyst for systemic inflammation body, which contribute to emergence various brain disorders. The identification several genes associated with PD, well their connection neuroinflammation, raises likelihood susceptibility. Moreover, advancing age mitochondrial weaken system, potentially implicating them onset disease, particularly among older Compromised integrity blood–brain barrier could facilitate system’s access tissue. exposure lead encounters native antigens or infections, triggering an autoimmune response. Furthermore, there is mounting evidence supporting notion gut dysbiosis might represent initial trigger inflammation, ultimately promoting neurodegeneration. In comprehensive review, we will delve into numerous hypotheses surrounding role both innate adaptive immunity PD.

Язык: Английский

Процитировано

10
RGS10 attenuates systemic immune dysregulation induced by chronic inflammatory stress DOI Creative Commons
Janna Jernigan, Hannah A. Staley,

Zachary Baty

и другие.

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Фев. 24, 2025

Abstract Regulator of G-protein signaling 10 (RGS10), a key homeostatic regulator immune cells, has been implicated in multiple diseases associated with aging and chronic inflammation including Parkinson’s Disease (PD). Interestingly, subjects idiopathic PD display reduced levels RGS10 subsets peripheral cells. Additionally, individuals have shown to increased activated cells cerebrospinal fluid (CSF) compared age-matched healthy controls. However, it is unknown whether the CSF also exhibit decreased RGS10. Utilizing Michael J. Fox Foundation Progression Markers Initiative (PPMI) study we found that are controls prodromal individuals. As circulating PD, hypothesized regulates cell responses systemic (CSI) prior onset neurodegeneration. To test this, induced CSI for 6 weeks C57BL6/J mice KO assess CNS-associated responses. We deficiency synergizes induce bias inflammatory cytotoxic populations, reduction antigen presentation machinery blood as well around brain most notable males. These results highlight an important response implicate potential contributor development dysregulation PD.

Язык: Английский

Процитировано

0
A single-cell atlas to map sex-specific gene-expression changes in blood upon neurodegeneration DOI Creative Commons
Friederike Grandke, Tobias Fehlmann, Fabian Kern

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 25, 2025

Abstract The clinical course and treatment of neurodegenerative disease are complicated by immune-system interference chronic inflammatory processes, which remain incompletely understood. Mapping immune signatures in larger human cohorts through single-cell gene expression profiling supports our understanding observed peripheral changes neurodegeneration. Here, we employ over 909k blood mononuclear cells (PBMCs) from 121 healthy individuals, 48 patients with mild cognitive impairment (MCI), 46 Parkinson’s (PD), 27 Alzheimer’s (AD), 15 both PD MCI. dataset is interactively accessible a freely available website ( https://www.ccb.uni-saarland.de/adrcsc ). In this work, identify disease-associated cell type composition the sex-specific manner, offering insights into solid tissue AD PD.

Язык: Английский

Процитировано

0
Frequencies of Circulating Immune Cells in Patients with Parkinson’s Disease: Correlation with MDS-UPDRS Scores DOI Creative Commons
David Goldeck,

Lilly Oettinger,

Tamàs Fülöp

и другие.

Journal of Integrative Neuroscience, Год журнала: 2025, Номер 24(2)

Опубликована: Фев. 21, 2025

Background: Parkinson’s Disease (PD) is associated with dysregulated/chronic inflammation. The immune system has multiple roles including beneficial effects such as clearing alpha synuclein aggregates. However, peripheral cells entering the brain may also contribute to inflammation and neurodegeneration. To identify which might have a negative impact could be potential therapeutic targets, we compared signatures of patients healthy controls. Methods: Multicolor flow cytometry was used determine frequencies major cell subsets in blood mononuclear (PBMCs) PD Because Cytomegalovirus (CMV) infection on distribution subsets, particularly cluster differentiation (CD)8+ T-cells, all participants were tested for CMV seropositivity. Results: Although cohort 35 exhibited well-established T-cell signature driven by infection, there no differences differentiated or pro-inflammatory B-cells natural killer (NK-cells) attributable disease. percentages myeloid-derived suppressor (MDSCs) higher than Moreover, CD14+CD16+ (intermediate) monocytes expressing C-C chemokine receptor type 5 (CCR5) correlated disease severity assessed Movement Disorder Society’s revised version Unified Rating Scale (MDS-UPDRS) score duration. Conclusions: A comprehensive evaluation circulating revealed myeloid between controls some correlation monocyte abundance severity.

Язык: Английский

Процитировано

0
Sex-specific immune-biological profiles in Parkinson's disease DOI Creative Commons

Roberta Bovenzi,

Matteo Conti,

Clara Simonetta

и другие.

Journal of Neuroimmunology, Год журнала: 2025, Номер unknown, С. 578610 - 578610

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Peripheral-central immune crosstalk in Parkinson’s disease and its association with clinical severity DOI Creative Commons
Julia C. Greenland, Jonathan Holbrook,

Lakmini Kahanawita

и другие.

Brain Behavior and Immunity, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease DOI Open Access
Jasna Šaponjić, Rebeca Mejı́as, Neda Nikolovski

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(8), С. 4330 - 4330

Опубликована: Апрель 14, 2024

Parkinson's disease (PD) is a chronic, age-related, progressive multisystem associated with neuroinflammation and immune dysfunction. This review discusses the methodological approaches used to study changes in central peripheral immunity PD, advantages limitations of techniques, their applicability humans. Although single animal model cannot replicate all pathological features human disease, present most models PD plays critical role understanding involvement system (IS) pathogenesis PD. The IS its interactions different cell types nervous (CNS) play an important Even though culture do not fully reflect complexity progression, they are limited ability mimic long-term effects need validation through vivo studies. They indispensable tool for interplay between this disease. Understanding immune-mediated mechanisms may lead potential therapeutic targets treatment We believe that development guidelines experiments patients crucial ensure validity consistency results.

Язык: Английский

Процитировано

3
Inflammation and heterogeneity in synucleinopathies DOI Creative Commons
Antoine Freuchet,

Anaëlle Pinçon,

A Sette

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Авг. 30, 2024

Neurodegenerative diseases represent a huge healthcare challenge which is predicted to increase with an aging population. Synucleinopathies, including Parkinson's disease (PD), dementia Lewy bodies (DLB), and multiple system atrophy (MSA), present complex challenges in understanding their onset progression. They are characterized by the abnormal aggregation of α-synuclein brain leading neurodegeneration. Accumulating evidence supports existence distinct subtypes based on site initiation, genetics, and, more recently, neuroinflammation. Mediated both central nervous system-resident cells, peripheral immune gut dysbiosis, neuroinflammation appears as key process progression neuronal loss. Sex-based differences add another layer complexity synucleinopathies, influencing prevalence - known higher incidence PD males compared females well phenotype responses. Biological sex affects neuroinflammatory pathways response, suggesting need for sex-specific therapeutic strategies biomarker identification. Here, we review heterogeneity describing etiology, mechanisms inflammatory processes contribute pathology, consideration sex-based highlight personalized therapeutics.

Язык: Английский

Процитировано

3
Age-Related Adaptive Immune Changes in Parkinson’s Disease DOI Creative Commons
Antonina Kouli, Caroline H. Williams‐Gray

Journal of Parkinson s Disease, Год журнала: 2022, Номер 12(s1), С. S93 - S104

Опубликована: Июнь 3, 2022

Ageing is a major risk factor for most neurodegenerative diseases, including Parkinson's disease (PD). Progressive age-related dysregulation of the immune system termed immunosenescence and responsible weakened response to novel antigens, increased susceptibility infections reduced effectiveness vaccines seen in elderly. Immune activation, both within brain periphery, heavily implicated PD but role has not been fully explored. Studies date provide some evidence an attenuation PD, particularly reduction senescent CD8 T lymphocytes cases compared similarly aged controls. Here, we discuss recent abnormalities with focus on cell senescence explore their potential pathogenesis development.

Язык: Английский

Процитировано

11