Exploring the relationship betweenGBA1host genotype and gut microbiome in theGBA1L444P/WTmouse model: Implications for Parkinson disease pathogenesis DOI Creative Commons
Elisa Menozzi,

Mallia Geiger,

Victoria Meslier

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 15, 2024

Abstract Background Heterozygous variants in GBA1 are the commonest genetic risk factor for Parkinson disease (PD) but penetrance is incomplete. dysfunction can cause gastrointestinal disturbances and microbiome changes preclinical models. Mounting evidence suggests that microbiota-gut-brain axis potentially implicated PD pathogenesis. Whether gut composition influenced by host genetics heterozygosis has never been explored. Objectives To evaluate whether heterozygosity pathogenic L444P variant perturbations composition. Methods Faecal samples collected from L444P/WT WT/WT mice at 3 6 months of age were analysed through shotgun metagenomic sequencing. Results No differences α- β-diversity detected between genotyped groups, either time points. Overall, we found a little variation functional potential over time. Conclusion Host genotype does not impact structure presented mouse model. Studies investigating effect second hit on physiology could explain partial PD.

Language: Английский

α-Synuclein pathology as a target in neurodegenerative diseases DOI

Hye-Jin Park,

Tae‐In Kam, Valina L. Dawson

et al.

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

Language: Английский

Citations

4
Prodromal Parkinson’s Disease DOI
Iro Boura, Karolina Popławska-Domaszewicz,

Naomi Limbachiya

et al.

Neurologic Clinics, Journal Year: 2025, Volume and Issue: 43(2), P. 209 - 228

Published: Jan. 22, 2025

Language: Английский

Citations

0
Brain Glycogen—Its Metabolic Role in Neuronal Health and Neurological Disorders—An Extensive Narrative Review DOI Creative Commons
Ana Isabel Beltrán-Velasco

Metabolites, Journal Year: 2025, Volume and Issue: 15(2), P. 128 - 128

Published: Feb. 13, 2025

Background: Brain glycogen is imperative for neuronal health, as it supports energy demands and metabolic processes. This review examines the pathways involved in storage utilization central nervous system, emphasizing their role both physiology pathology. It explores how alterations metabolism contribute to neurological disorders, including neurodegenerative diseases, epilepsy, conditions while highlighting bidirectional interaction between neurons glia maintaining brain homeostasis. Methods: A comprehensive search of articles published 2015 2025 was conducted using following databases: ScienceDirect, Scopus, Wiley, Web Science, Medline, PubMed. The selection relevant studies based on focus its conditions, with that did not meet inclusion criteria being excluded. Results: processes are subject rigorous regulation by astrocyte-neuron interactions, thereby ensuring homeostasis availability. dysregulation mobilization has been implicated development synaptic dysfunction, excitotoxicity, neurodegeneration a variety disorders. For instance, aberrant accumulation diseases such Lafora disease associated severe neurodegeneration, impaired shown exacerbate deficits Alzheimer's epilepsy. Conclusions: Targeting represents promising approach therapeutic intervention However, translation these strategies human models remains challenging, particularly regard long-term safety specificity glycogen-targeted therapies.

Language: Английский

Citations

0
Organic solvents and neurodegenerative diseases: Exploring a possible link DOI
Mary Beth Genter

Advances in neurotoxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
The Gut‐Brain Axis in Parkinson disease: Emerging Concepts and Therapeutic Implications DOI Creative Commons
Elisa Menozzi, Anthony H.V. Schapira, Per Borghammer

et al.

Movement Disorders Clinical Practice, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract Background The gut‐brain axis, i.e. the bidirectional communication system between gut and brain, has become of central importance in Parkinson disease (PD) research over past 20 years. Aims We aimed to describe milestones axis PD development theories proposing involvement gastrointestinal tract pathogenesis. Methods searched PubMed using terms ‘gut‐brain axis’ AND ‘Parkinson disease’, selected relevant articles provide foundation for reconstructing an historical overview PD. Results Mounting evidence from preclinical, clinical post‐mortem studies suggests that a subgroup patients present with range prodromal symptoms (e.g., autonomic dysfunction, rapid eye movement sleep behaviour disorder) which reflect initial accumulation later spread pathological α‐synuclein rostrally (“body‐first” PD). Through neural connections along may producing clinically manifest disease. Recently, two mechanisms involving have attracted increasing attention their role pathogenesis progression, namely perturbation composition microorganisms living (the microbiome), dysfunction enteroendocrine cells. Conclusion Treatments targeting especially microbiome cells pathway, could potentially slow progression or even prevent onset. Among these, pre/probiotics, faecal microbiota transplantation, glucagon‐like peptide‐1 receptor agonists, entered advanced stages trials humans shown potential symptomatic disease‐modifying effects.

Language: Английский

Citations

0
A life course approach to neurodegeneration DOI
Sarah‐Naomi James, Jonathan M. Schott, Yoav Ben‐Shlomo

et al.

Oxford University Press eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 209 - 228

Published: Feb. 20, 2025

Abstract Neurodegenerative diseases typically have their onset in later life and reflect varying combinations of genetic risk course exposures. In this chapter, we consider the contribution that epidemiological approaches can make to our understanding neurodegenerative disorders, with particular reference Alzheimer’s disease Parkinson’s disease. These two diseases, as well others, are characterized by accumulation misfolded proteins within central nervous system leading neuronal cell death. Conceptual issues discussed, including reserve resilience, methodological challenges determining for where vivo diagnosis is imprecise time between potential exposures manifestations may be many decades. Evidence linking conditions presented, a focus on diverse populations implications prevention strategies.

Language: Английский

Citations

0
Environmental exposures and familial background alter the induction of neuropathology and inflammation after SARS-CoV-2 infection DOI Creative Commons
Debotri Chatterjee, Drishya Kurup, Richard J. Smeyne

et al.

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 23, 2025

Language: Английский

Citations

0
Infections in the Etiology of Parkinson’s Disease and Synucleinopathies: A Renewed Perspective, Mechanistic Insights, and Therapeutic Implications DOI Creative Commons
Gabriela Mercado,

Christopher Kaeufer,

Franziska Richter

et al.

Journal of Parkinson s Disease, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 29

Published: Sept. 25, 2024

Increasing evidence suggests a potential role for infectious pathogens in the etiology of synucleinopathies, group age-related neurodegenerative disorders including Parkinson’s disease (PD), multiple system atrophy and dementia with Lewy bodies. In this review, we discuss link between infections synucleinopathies from historical perspective, present emerging that supports link, address current research challenges focus on neuroinflammation. Infectious can elicit neuroinflammatory response modulate genetic risk PD related synucleinopathies. The mechanisms how might be linked as well overlap immune cellular pathways affected by virulent disease-related factors are discussed. Here, an important α-synuclein against is emerging. Critical methodological knowledge gaps addressed, provide new future perspectives to these gaps. Understanding neuroinflammation influence will essential development early diagnostic tools novel therapies.

Language: Английский

Citations

3
Alpha Synuclein Induced Immune Response Triggers Parkinson's Disease Like Symptoms DOI Creative Commons

Rebekah G. Parkinson,

Tony Xu,

Martin Jacob

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

SUMMARY Increasing evidence suggests that Parkinson’s disease is an autoimmune disorder, with findings of elevated peripheral blood mononuclear cell in patients, and antigenic properties α-synuclein driving both the innate adaptive immunity. Yet, how interaction a specific immune response participates to ontogenesis has remained unanswered. Here, we reveal antigen underlies disease. We demonstrate autoimmunity mediated by CD4+T activation α-syn 61-75 required lead infiltration localized inflammation substantia nigra, triggering dopaminergic neurodegeneration deficits locomotion gait kinematics. This study offers first immune-induced mouse model recapitulates all features mechanisms onset. It provides basis for temporally tracking symptom development, exploring preventive strategies prodromal therapeutic interventions Disease. In brief Peripheral immunization causes disease-like symptoms mice. Highlights - Both CD4+ T cells are essential ontogenesis. injection induces significant brain. associated inflammation, aggregation loss nigra pars compacta. Levodopa-sensitive motor detected 8 weeks following novel induced

Language: Английский

Citations

2
No association between genetically predicted vitamin D levels and Parkinson’s disease DOI Creative Commons

Zihao Wang,

Huan Xia,

Yunfa Ding

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(11), P. e0313631 - e0313631

Published: Nov. 15, 2024

Background Parkinson’s disease (PD) is a neurodegenerative disorder, primarily characterized by motor impairments. Vitamin D has several regulatory functions in nerve cell survival and gene expression via its receptors. Although research shown that vitamin deficiency prevalent among PD patients, the causal link to risk remains unclear. This study aims investigate relationship between using bidirectional two-sample Mendelian randomization (MR) analysis method. Methods applied MR explore PD. We selected statistically significant single nucleotide polymorphisms (SNPs) related 25-hydroxyvitamin (25(OH)D) as instrumental variables (IVs), ensuring no association with known confounders. The used GWAS data from over 1.2 million Europeans across four major published datasets, elucidating genetic correlation levels Results identified 148 SNPs associated 25(OH)D. After adjustment for confounding-related SNPs, 131 remained analysis. Data three cohorts revealed 25(OH)D IVW method ( P cohort1 = 0.365, cohort2 0.525, cohort3 0.117). reverse indicated insufficient evidence of causing decreased 0.776). Conclusion first use results indicate are not significantly causally at level. Therefore, future studies should exercise caution when investigating risk. While direct exists PD, this does preclude potential biomarker diagnosis. Furthermore, larger-scale longitudinal necessary evaluate diagnostic predictive value

Language: Английский

Citations

2