Neurochemistry International, Год журнала: 2024, Номер 177, С. 105760 - 105760
Опубликована: Май 7, 2024
Язык: Английский
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Янв. 29, 2024
Background There is increasing evidence that the types of immune cells are associated with various neurodegenerative diseases. However, it currently unclear whether these associations reflect causal relationships. Objective To elucidate relationship between and diseases, we conducted a two-sample Mendelian randomization (MR) analysis. Materials methods The exposure outcome GWAS data used in this study were obtained from an open-access database ( https://gwas.mrcieu.ac.uk/ ), employed MR analysis to assess 731 cell features four including Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS) multiple (MS). All was Multiple minimize bias obtain reliable estimates variables interest outcomes. Instrumental variable selection criteria restricted ensure accuracy effectiveness species risk Results identified potential relationships different Specifically, found 8 have AD, 1 type has PD, 6 ALS, MS. Conclusion Our study, through genetic means, demonstrates close specific ALS MS, providing useful guidance for future clinical researches.
Язык: Английский
Процитировано
20
npj Parkinson s Disease, Год журнала: 2025, Номер 11(1)
Опубликована: Янв. 3, 2025
Язык: Английский
Процитировано
4
Acta Neuropathologica Communications, Год журнала: 2021, Номер 9(1)
Опубликована: Фев. 25, 2021
Abstract Pain is a common non-motor symptom of Parkinson’s disease (PD), with current limited knowledge its pathophysiology. Here, we show that peripheral inoculation mouse alpha-synuclein (α-Syn) pre-formed fibrils, in transgenic model PD, elicited retrograde trans-synaptic spreading α-Syn pathology (pSer129) across sensory neurons and dorsal nerve roots, reaching central pain processing regions, including the spinal horn projections anterolateral system nervous (CNS). Pathological to CNS propagation aggregates along interconnected neuronal populations within afferents, was concomitant impaired nociceptive response, reflected by mechanical allodynia, reduced conduction velocities (sensory motor) degeneration small- medium-sized myelinated fibers. Our findings link between transneuronal neuron dysfunction neuropathic impairment, suggesting promising avenues investigation into mechanisms underlying PD.
Язык: Английский
Процитировано
59
Journal of Neuroinflammation, Год журнала: 2022, Номер 19(1)
Опубликована: Июнь 6, 2022
Circadian disturbance is a common nonmotor complaint in Parkinson's disease (PD). The molecular basis underlying circadian rhythm PD poorly understood. Neuroinflammation has been identified as key contributor to pathology. In this study, we explored the potential link between core clock molecule Rev-erbα and microglia-mediated NLR family pyrin domain-containing 3 (NLRP3) inflammasome pathogenesis.We first examined diurnal rhythms changes inflammatory cytokines expression SN of MPTP-induced mice. Further, used BV2 cell investigate impacts on NLRP3 microglial polarization induced by 1-methyl-4-phenylpyridinium (MPP+) αsyn pre-formed fibril. role regulating activation via NF-κB pathway was then explored. Effects SR9009 against activation, microgliosis nigrostriatal dopaminergic degeneration striatum mice were studied detail.BV2 cell-based experiments revealed through pathways. oscillation gene substantia nigra (SN) disappeared mice, well morphology. significantly elevated. Furthermore, neurons loss system partially reversed SR9009, selective agonist. addition, effectively reduced glial system.These observations suggest that protein plays an essential attenuating neuroinflammation pathology, provides therapeutic target for treatment.
Язык: Английский
Процитировано
59
Biomolecules, Год журнала: 2022, Номер 12(2), С. 329 - 329
Опубликована: Фев. 18, 2022
Progress in developing disease-modifying therapies Parkinson's disease (PD) can only be achieved through reliable objective markers that help to identify subjects at risk. This includes an early and accurate diagnosis as well continuous monitoring of progression therapy response. Although PD still relies mainly on clinical features, encouragingly, advances biomarker discovery have been made. The cerebrospinal fluid (CSF) is a biofluid particular interest study biomarkers since it closest the brain structures therefore could serve ideal source reflect ongoing pathologic processes. According key pathophysiological mechanisms, CSF status α-synuclein species, amyloid tau pathology, neurofilament light chain, lysosomal enzymes neuroinflammation provide promising preliminary results candidate biomarkers. Untargeted approaches field metabolomics insights into novel interconnected biological pathways. Markers based genetic forms contribute identifying subgroups suitable for gene-targeted treatment strategies might also transferable sporadic PD. Further validation analyses large cohort studies will or combinations with best value research purposes.
Язык: Английский
Процитировано
53
Current Neurology and Neuroscience Reports, Год журнала: 2022, Номер 22(8), С. 427 - 440
Опубликована: Июнь 8, 2022
Abstract Purpose of Review Neuroinflammation plays a significant role in Parkinson’s disease (PD) etiology along with mitochondrial dysfunction and impaired proteostasis. In this context, mechanisms related to immune response can act as modifiers at different steps the neurodegenerative process justify growing interest anti-inflammatory agents potential disease-modifying treatments PD. The discovery inherited gene mutations PD has allowed researchers develop cellular animal models study underlying biology, but original cause neuroinflammation is still debated date. Recent Findings Cell autonomous alterations neuronal cells, including damage protein aggregation, could play role, recent findings also highlighted importance intercellular communication both local systemic level. This given rise debate about non-neuronal cells reignited intense research into gut-brain axis other interactions development disease. Whatever trigger PD, what appears quite clear that aberrant activation glial components system creates vicious circle which neurodegeneration nourish each other. Summary review, we will provide an up-to-date summary main those induced by environmental factors (e.g. gut microbiome) genetic background affected patients. Starting from lesson provided familial forms discuss pathophysiological linked inflammation idiopathic forms. Finally, comment on clinical translatability immunobiomarkers identified patient cohorts update current therapeutic strategies aimed overcoming or preventing
Язык: Английский
Процитировано
53
Journal of Parkinson s Disease, Год журнала: 2022, Номер 12(s1), С. S183 - S200
Опубликована: Июнь 3, 2022
Given the clear role of inflammation in pathogenesis Parkinson's disease (PD) and its impact on incidence phenotypical characteristics, this review provides an overview with focus inflammatory biofluid markers blood cerebrospinal fluid (CSF) PD patient cohorts. In preparation for clinical trials targeting immune system, we specifically address following questions: 1) What evidence do have pro-inflammatory profiles CSF sporadic genetic patients? 2) Is there a anti-inflammatory mediators blood/CSF? 3) Do reflect those indicative cross-talk between periphery brain? 4) blood/CSF change over course as assessed repeatedly taken biosamples? 5) Are associated trajectories PD? 6) levels neurodegenerative/PD-specific biomarkers? Knowledge these questions will inform future strategies stratification cohort enrichment well suitable outcome measures trials.
Язык: Английский
Процитировано
46
Glia, Год журнала: 2022, Номер 71(3), С. 571 - 587
Опубликована: Ноя. 10, 2022
Inflammation is a common feature in neurodegenerative diseases that contributes to neuronal loss. Previously, we demonstrated the basal inflammatory tone differed between brain regions and, consequently, reaction generated pro-inflammatory stimulus was different. In this study, assessed innate immune midbrain and striatum using an experimental model of Parkinson's disease. An adeno-associated virus serotype 9 expressing α-synuclein mCherry genes or gene administered into substantia nigra. Myeloid cells (CD11b+ ) astrocytes (ACSA2+ were purified from for bulk RNA sequencing. parkinsonian midbrain, CD11b+ presented unique anti-inflammatory transcriptomic profile degenerative microglia signatures described models other conditions. By contrast, striatal showed state similar disease-associated microglia. prominent increase infiltrated monocytes/macrophages observed together with microglia, participated actively phagocytosis dopaminergic bodies. Although phagocytic profile, morphology cell density preserved no active detected. Interestingly, fingerprint low number differentially displayed transcripts striatum. During α-synuclein-dependent degeneration, experience context-dependent activation states different contribution reaction. Our results point towards relevance selecting appropriate targets design neuroprotective strategies aimed modulate system during phase degeneration.
Язык: Английский
Процитировано
43
Translational Neurodegeneration, Год журнала: 2023, Номер 12(1)
Опубликована: Янв. 30, 2023
Abstract The impact of coronavirus disease 2019 (COVID-19) pandemic on patients with neurodegenerative diseases and the specific neurological manifestations COVID-19 have aroused great interest. However, there are still many issues concern to be clarified. Therefore, we review current literature complex relationship between an emphasis Parkinson’s (PD) Alzheimer’s (AD). We summarize infection symptom severity, progression, mortality rate PD AD, discuss whether could trigger AD. In addition, susceptibility prognosis in AD also included. order achieve better management patients, modifications care strategies, drug therapies, vaccines during listed. At last, mechanisms underlying link reviewed.
Язык: Английский
Процитировано
32
Movement Disorders, Год журнала: 2023, Номер 38(7), С. 1143 - 1155
Опубликована: Май 8, 2023
The endotoxin hypothesis of Parkinson's disease (PD) is the idea that lipopolysaccharide (LPS) endotoxins contribute to pathogenesis this disorder. LPS are found in, and released from, outer membrane Gram-negative bacteria, for example in gut. It proposed gut dysfunction early PD leads elevated levels wall blood, which promotes both α-synuclein aggregation enteric neurons a peripheral inflammatory response. Communication brain via circulating cytokines blood and/or gut-brain axis neuroinflammation spreading pathology, exacerbating neurodegeneration brainstem nuclei loss dopaminergic substantia nigra, manifesting clinical symptoms PD. evidence supporting includes: (1) dysfunction, permeability, bacterial changes occur PD, (2) serum increased proportion patients, (3) induces expression, aggregation, neurotoxicity, (4) causes activation monocytes leading cytokine production, (5) inflammation specific midbrain neurons, mediated by microglia. If correct, then treatment options might include: changing microbiome, reducing levels, or blocking response immune cells microglia LPS. However, has number limitations requires further testing, particular whether can reduce incidence, progression, severity. © 2023 Authors. Movement Disorders published Wiley Periodicals LLC on behalf International Parkinson Disorder Society.
Язык: Английский
Процитировано
32