Infiltrating CD8+ T cells exacerbate Alzheimer’s disease pathology in a 3D human neuroimmune axis model

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(9), P. 1489 - 1504

Published: Aug. 24, 2023

Language: Английский

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RNAi-based drug design: considerations and future directions

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(5), P. 341 - 364

Published: April 3, 2024

Language: Английский

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Microglia regulation of central nervous system myelin health and regeneration

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 24(1), P. 49 - 63

Published: July 14, 2023

Language: Английский

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Aging microglia

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(5)

Published: April 21, 2023

Abstract Microglia are the tissue-resident macrophage population of brain, specialized in supporting CNS environment and protecting it from endogenous exogenous insults. Nonetheless, their function declines with age, ways that remain to be fully elucidated. Given critical role played by microglia neurodegenerative diseases, a better understanding aging phenotype is an essential prerequisite designing preventive therapeutic strategies. In this review, we discuss most recent literature on aging, comparing findings rodent models human subjects.

Language: Английский

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Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(3), P. 409 - 420

Published: Feb. 16, 2024

Language: Английский

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Cellular architecture of evolving neuroinflammatory lesions and multiple sclerosis pathology

Cell, Journal Year: 2024, Volume and Issue: 187(8), P. 1990 - 2009.e19

Published: March 20, 2024

Multiple sclerosis (MS) is a neurological disease characterized by multifocal lesions and smoldering pathology. Although single-cell analyses provided insights into cytopathology, evolving cellular processes underlying MS remain poorly understood. We investigated the dynamics of modeling temporal regional rates progression in mouse experimental autoimmune encephalomyelitis (EAE). By performing spatial expression profiling using situ sequencing (ISS), we annotated neighborhoods found centrifugal evolution active lesions. demonstrated that disease-associated (DA)-glia arise independently are dynamically induced resolved over course. Single-cell mapping human archival spinal cords confirmed differential distribution homeostatic DA-glia, enabled deconvolution inactive sub-compartments, identified new lesion areas. establishing resource neuropathology at resolution, our study unveils intricate MS.

Language: Английский

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The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 23, 2024

Abstract Ageing is a crucial risk factor for Alzheimer’s disease (AD) and characterised by systemic changes in both intracellular extracellular microenvironments that affect the entire body instead of single organ. Understanding specific mechanisms underlying role ageing development can facilitate treatment ageing-related diseases, such as AD. Signs brain have been observed AD patients animal models. Alleviating pathological caused dramatically ameliorate amyloid beta- tau-induced neuropathological memory impairments, indicating plays pathophysiological process In this review, we summarize impact several age-related factors on propose preventing promising strategy improving cognitive health.

Language: Английский

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Oligodendrocyte–axon metabolic coupling is mediated by extracellular K+ and maintains axonal health

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(3), P. 433 - 448

Published: Jan. 24, 2024

The integrity of myelinated axons relies on homeostatic support from oligodendrocytes (OLs). To determine how OLs detect axonal spiking and rapid axon-OL metabolic coupling is regulated in the white matter, we studied activity-dependent calcium (Ca

Language: Английский

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STING orchestrates the neuronal inflammatory stress response in multiple sclerosis

Cell, Journal Year: 2024, Volume and Issue: 187(15), P. 4043 - 4060.e30

Published: June 14, 2024

Inflammation-induced neurodegeneration is a defining feature of multiple sclerosis (MS), yet the underlying mechanisms remain unclear. By dissecting neuronal inflammatory stress response, we discovered that neurons in MS and its mouse model induce stimulator interferon genes (STING). However, activation STING requires detachment from stromal interaction molecule 1 (STIM1), process triggered by glutamate excitotoxicity. This initiates non-canonical signaling, which leads to autophagic degradation glutathione peroxidase 4 (GPX4), essential for redox homeostasis thereby inducing ferroptosis. Both genetic pharmacological interventions target protect against inflammation-induced neurodegeneration. Our findings position as central regulator detrimental integrating inflammation with signaling cause cell death, present it tractable treating MS.

Language: Английский

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Cellular senescence, DNA damage, and neuroinflammation in the aging brain

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: 47(6), P. 461 - 474

Published: May 9, 2024

Language: Английский

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