Human Motor Neurons Elicit Pathological Hallmarks of ALS and Reveal Potential Biomarkers of the Disease in Response to Prolonged IFNγ Exposure

Journal of Neuroscience, Год журнала: 2024, Номер unknown, С. e1787232024 - e1787232024

Опубликована: Фев. 27, 2024

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disorder marked by progressive motor neuron degeneration and muscle denervation. A recent transcriptomic study integrating wide range of human ALS samples revealed that the upregulation p53, downstream target inflammatory stress, commonly detected in familial sporadic cases mechanism linked to transactive response DNA-binding protein 43 (TDP-43) dysfunction. In this study, we show prolonged interferon-gamma (IFNγ) treatment induced pluripotent stem cell-derived spinal neurons results severe cytoplasmic aggregation TDP-43. TDP-43 dysfunction resulting from either IFNγ exposure or an ALS-associated mutation was associated with activation p53 pathway. This accompanied hyperactivation neuronal firing, followed complete loss their electrophysiological function. Through comparative single-cell transcriptome analysis, have identified significant alterations genes exposed IFNγ, implicating direct involvement pathology. Interestingly, found induce levels programmed death-ligand 1 (PD-L1) expression without affecting any other immune checkpoint proteins. finding suggests potential role excessive PD-L1 development, given recently reported impair firing ability mice. Our findings suggest exposing could directly derive pathogenesis, even presence inherent genetic functional glia component. Furthermore, provides comprehensive list candidate for future immunotherapeutic targets which treat forms ALS, account 90% all cases.

Язык: Английский

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The immunomodulatory mechanism of acupuncture treatment for ischemic stroke: research progress, prospects, and future direction

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Май 2, 2024

Ischemic stroke (IS) is one of the leading causes death and disability. Complicated mechanisms are involved in pathogenesis IS. Immunomodulatory crucial to Acupuncture a traditional non-drug treatment that has been extensively used treat The exploration neuroimmune modulation will broaden understanding underlying acupuncture treatment. This review summarizes immune response cells, cytokines, organs after an immunomodulatory on central nervous system peripheral immunity, as well factors influence effects treatment, were summarized. We suggest prospects future directions for research IS based current progress, we hope these provide inspiration researchers. Additionally, shown favorable outcomes immune-based diseases, generating new possible targets treatments diseases.

Язык: Английский

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Differentiation and regulation of CD4+ T cell subsets in Parkinson’s disease

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Авг. 17, 2024

Parkinson's disease (PD) is the second most common neurodegenerative disease, and its hallmark pathological features are loss of dopaminergic (DA) neurons in midbrain substantia nigra pars compacta (SNpc) accumulation alpha-synuclein (α-syn). It has been shown that integrity blood-brain barrier (BBB) damaged PD patients, a large number infiltrating T cells inflammatory cytokines have detected cerebrospinal fluid (CSF) brain parenchyma patients animal models, including significant change proportion different CD4

Язык: Английский

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A systematic review and meta-analysis of pteridines in mild cognitive impairment and Alzheimer’s disease

BMC Geriatrics, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 13, 2025

Язык: Английский

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IDO1 modulates pain sensitivity and comorbid anxiety in chronic migraine through microglial activation and synaptic pruning

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

Опубликована: Фев. 18, 2025

Язык: Английский

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