Circulating senescent myeloid cells infiltrate the brain and cause neurodegeneration in histiocytic disorders.

ABSTRACT: Neurodegenerative diseases (ND) are characterized by progressive loss of neuronal function. Mechanisms of ND pathogenesis are incompletely understood, hampering the development of effective therapies. Langerhans cell histiocytosis (LCH) is an inflammatory neoplastic disorder caused by hematopoietic progenitors expressing mitogen-activated protein kinase (MAPK)-activating mutations that differentiate into senescent myeloid cells that drive lesion formation. Some individuals with LCH subsequently develop progressive and incurable neurodegeneration (LCH-ND). Here, we showed that LCH-ND was caused by myeloid cells that were clonal with peripheral LCH cells. Circulating BRAFV600E⁺ myeloid cells caused the breakdown of the blood-brain barrier (BBB), enhancing migration into the brain

SUBMITTER: Wilk CM 

PROVIDER: S-EPMC11587932 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature