Senescent-like microglia limit remyelination through the senescence associated secretory phenotype

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 7, 2025

The capacity to regenerate myelin in the central nervous system diminishes with age. This decline is particularly evident multiple sclerosis (MS), a chronic demyelinating disease. Whether cellular senescence, hallmark of aging, contributes remyelination impairment remains unknown. Here, we show that senescent cells accumulate within demyelinated lesions after injury, and treatments senolytics enhances young middle-aged mice but not aged mice. In mice, observe upregulation senescence-associated transcripts, primarily microglia macrophages, demyelination, followed by reduction during remyelination. However, factors persist lesions, correlating inefficient Proteomic analysis secretory phenotype (SASP) reveals elevated levels CCL11/Eotaxin-1 which found inhibit oligodendrocyte maturation. These results suggest therapeutic targeting SASP components, such as CCL11, may improve aging MS. impact on authors treatment following demyelination young, these effects are mediated including CCL11.

Язык: Английский

Brain organoid methodologies to explore mechanisms of disease in progressive multiple sclerosis

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Дек. 18, 2024

Multiple sclerosis (MS), a debilitating autoimmune disorder targeting the central nervous system (CNS), is marked by relentless demyelination and inflammation. Clinically, it presents in three distinct forms: relapsing-remitting MS (RRMS), primary progressive (PPMS), secondary (SPMS). While disease-modifying therapies (DMTs) offer some relief to people with RRMS, treatment options for (pMS) remain frustratingly inadequate. This gap highlights an urgent need advanced disease modeling techniques unravel intricate pathology of pMS. Human induced pluripotent stem cell (iPSC) technologies brain organoids are emerging as promising tools both 2D 3D

Язык: Английский

All roads lead to cholesterol: Modulating lipid biosynthesis in multiple sclerosis patient-derived models

Cell stem cell, Год журнала: 2024, Номер 31(11), С. 1551 - 1552

Опубликована: Ноя. 1, 2024