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

et al.

Published: Nov. 6, 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 in-flammation body, which contribute to emergence various brain disorders. The identification several genes associated with PD, well their connection neuroinflamma-tion, raises likelihood susceptibility. Moreover, advancing age mitochondrial weaken system, potentially implicating them onset dis-ease, 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.

Language: Английский

The pathogenesis of Parkinson's disease DOI
Huw R. Morris, Maria Grazia Spillantini, Carolyn M. Sue

et al.

The Lancet, Journal Year: 2024, Volume and Issue: 403(10423), P. 293 - 304

Published: Jan. 1, 2024

Language: Английский

Citations

300
A systematic review and meta-analysis of inflammatory biomarkers in Parkinson’s disease DOI Creative Commons

Yi Qu,

Jiangting Li,

Qixiong Qin

et al.

npj Parkinson s Disease, Journal Year: 2023, Volume and Issue: 9(1)

Published: Feb. 4, 2023

Abstract Neuroinflammation plays a crucial role in the pathogenesis of Parkinson’s disease (PD), but controversies persist. Studies reporting concentrations blood or cerebrospinal fluid (CSF) markers for patients with PD and controls were included extracted. Pooled Hedges’g was adopted to illustrate comparisons, covariates used explore sources heterogeneity. Finally, 152 studies included. Increased IL-6, TNF-α, IL-1β, STNFR1, CRP, CCL2, CX3CL1, CXCL12 levels decreased INF-γ IL-4 noted group. In addition, increased CSF CRP CCL2 revealed compared controls. Consequently, significantly altered inflammatory verified between group control, suggesting that is accompanied by responses both peripheral CSF. This study registered PROSPERO, CRD42022349182.

Language: Английский

Citations

69
The role of inflammasomes in human diseases and their potential as therapeutic targets DOI Creative Commons
Jing Yao,

Keenan Sterling,

Zhe Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 5, 2024

Abstract Inflammasomes are large protein complexes that play a major role in sensing inflammatory signals and triggering the innate immune response. Each inflammasome complex has three components: an upstream sensor molecule is connected to downstream effector such as caspase-1 through adapter ASC. Inflammasome formation typically occurs response infectious agents or cellular damage. The active then triggers activation, followed by secretion of pro-inflammatory cytokines pyroptotic cell death. Aberrant activation activity contribute development diabetes, cancer, several cardiovascular neurodegenerative disorders. As result, recent research increasingly focused on investigating mechanisms regulate assembly well potential targeting inflammasomes treat various diseases. Multiple clinical trials currently underway evaluate therapeutic distinct inflammasome-targeting therapies. Therefore, understanding how different disease pathology may have significant implications for developing novel strategies. In this article, we provide summary biological pathological roles health disease. We also highlight key evidence suggests could be strategy new disease-modifying therapies effective conditions.

Language: Английский

Citations

66
Innate immune activation in neurodegenerative diseases DOI
Sergio Castro‐Gomez, Michael T. Heneka

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 790 - 814

Published: April 1, 2024

Language: Английский

Citations

21
Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus DOI Creative Commons
Clara Muñoz‐Castro, Marina Mejias‐Ortega,

Elisabeth Sánchez‐Mejías

et al.

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: Feb. 28, 2023

Microglia are brain-resident myeloid cells and play a major role in the innate immune responses of CNS pathogenesis Alzheimer's disease (AD). However, contribution nonparenchymal or brain-infiltrated to progression remains be demonstrated. Here, we show that monocyte-derived (MDC) invade brain parenchyma advanced stages AD continuum using transcriptional analysis immunohistochemical characterization post-mortem human hippocampus. Our findings demonstrated high proportion (60%) demented Braak V-VI individuals was associated with up-regulation genes rarely expressed by microglial abundant monocytes, among which stands membrane-bound scavenger receptor for haptoglobin/hemoglobin complexes Cd163. These Cd163-positive MDC invaded hippocampal parenchyma, acquired microglial-like morphology, were located close proximity blood vessels. Moreover, most interesting, these invading monocytes infiltrated nearby amyloid plaques contributing plaque-associated cell heterogeneity. aged-matched control pathology, no signs infiltration plaque invasion found. The previously reported degeneration/dysfunction hippocampus could key pathological factor inducing recruitment. data suggest clear association between endothelial activation turn may contribute damage barrier integrity. recruitment consequence rather than cause severity disease. Whether monocyte is beneficial detrimental pathology fully elucidated. open opportunity design targeted therapies, not only microglia but also peripheral population modulate provide better understanding immunological mechanisms underlying AD.

Language: Английский

Citations

35
The systemic immune response in Parkinson’s disease: focus on the peripheral immune component DOI Open Access

Johanne Lauritsen,

Marina Romero‐Ramos

Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 46(10), P. 863 - 878

Published: Aug. 17, 2023

Language: Английский

Citations

31
Immunological shifts during early-stage Parkinson’s disease identified with DNA methylation data on longitudinally collected blood samples DOI Creative Commons
Steven C. Pike, Matthew C. Havrda, Francesca Gilli

et al.

npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 11, 2024

Abstract Parkinson’s disease (PD) is the second most common neurodegenerative in United States. Decades before motor symptoms manifest, non-motor such as hyposmia and rapid eye movement (REM) sleep behavior disorder are highly predictive of PD. Previous immune profiling studies have identified alterations to proportions cells blood clinically defined PD patients. However, it remains unclear if these phenotypes manifest clinical diagnosis We utilized longitudinal DNA methylation (DNAm) microarray data from Progression Marker’s Initiative (PPMI) perform prodromal patients (Prod). previously reported changes neutrophil, monocyte, T cell numbers Additionally, we noted unrecognized decreases naive B compartment Prod patient group. Over time, observed proportion innate increased, but adaptive decreased. subsets associated with REM disturbances early cognitive decline. Lastly, increases memory both genetic ( LRRK2 genotype) infectious (cytomegalovirus seropositivity) risk factors Our analysis shows that peripheral system dynamic progresses. The study provides a platform understand how when occur whether intervention at particular stages may be therapeutically advantageous.

Language: Английский

Citations

9
Neuroinflammation and Immune Changes in Prodromal Parkinson’s Disease and Other Synucleinopathies DOI Creative Commons
Miriam Højholt Terkelsen, Ida Hyllen Klæstrup, Victor Schwartz Hvingelby

et al.

Journal of Parkinson s Disease, Journal Year: 2022, Volume and Issue: 12(s1), P. S149 - S163

Published: June 14, 2022

Multiple lines of clinical and pre-clinical research support a pathogenic role for neuroinflammation peripheral immune system dysfunction in Parkinson's disease. In this paper, we have reviewed summarised the published literature reporting evidence changes cohorts patients with isolated REM sleep behaviour disorder non-manifesting carriers GBA or LRRK2 gene mutations, who increased risk Parkinsonism synucleinopathies, could be prodromal stage these conditions. Taken together, findings studies suggest that early stages pathology involve activation both central systems significant crosstalk. We consider respect to those found disease discuss their possible pathological roles. Moreover, factors possibly associated response, such as immunomodulatory affected neurotransmitters gut-brain axis, are also considered.

Language: Английский

Citations

34
Sex differences in alpha-synucleinopathies: a systematic review DOI Creative Commons
Kausar Raheel,

Gemma Deegan,

Irene Di Giulio

et al.

Frontiers in Neurology, Journal Year: 2023, Volume and Issue: 14

Published: July 20, 2023

Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to suggestion neuroprotective properties female sex hormones (especially estrogen). The potential pathomechanisms any such effect on alpha-synucleinopathies, however, are far from understood. With that aim, we undertook systematically review, critically assess, contemporary evidence gender differences using bench-to-bedside approach.In this systematic studies investigating (Rapid Eye Movement (REM) Behavior Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) 2012 2022 were identified electronic database searches PubMed, Embase Ovid.One hundred sixty-two included; 5 RBD, 6 MSA, 20 DLB 131 PD studies. Overall, there is conclusive suggest sex-and gender-specific manifestation demographics, biomarkers, genetics, features, interventions, quality life alpha-synucleinopathies. Only limited data exists the effects distinct hormones, majority concentrating estrogen its speculated effects.Future disentangling underlying sex-specific mechanisms urgently needed order enable novel therapeutics.

Language: Английский

Citations

14
The major histocompatibility complex participates in Parkinson’s disease DOI Creative Commons

Rou Gu,

Jianyu Pan, Maher Un Nisa Awan

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107168 - 107168

Published: April 5, 2024

Parkinson's disease (PD) is a common neurodegenerative characterized by progressive loss of dopaminergic neurons in the substantia nigra and aggregation alpha-synuclein (α-syn). The central nervous system (CNS) has previously been considered as an immune-privileged area. However, studies have shown that immune responses are involved PD. major histocompatibility complex (MHC) presents antigens from Antigen-presenting cells(APCs) to T lymphocytes, will be induced. MHCs expressed microglia, astrocytes, neurons. Single nucleotide polymorphisms MHC related risk aggregated α-syn triggers expression activating glia cells. CD4+ CD8+ lymphocytes microglia activation detected brains PD patients. In addiction further increase blood-brain barrier (BBB) permeability cell infiltration Thus, through participating inflammatory responses.

Language: Английский

Citations

4