Inhibition of the Immunoproteasome Subunit LMP7 Ameliorates Cerebral White Matter Demyelination Possibly via TGFβ/Smad Signaling.

ABSTRACT:

Objectives

Chronic cerebral hypoperfusion induces white matter ischemic injury and cognitive impairment, whereas the mechanism remains unclear. Immunoproteasomes have been implicated in the pathogenesis of acute ischemia stroke and multiple sclerosis. However, the expression and role of immunoproteasomes in the brain of chronic cerebral hypoperfusion remain to be clarified.

Methods

Chronic white matter ischemic injury mice models were induced by bilateral carotid artery stenosis (BCAS). A selective immunoproteasome subunit low-molecular-mass peptide-7 (LMP7) inhibitor PR957 was administered to mice. Cognitive function, white matter integrity, and potential pathways were assessed after BCAS.

Results

The present study found that chronic cerebral hypoperfusion following

SUBMITTER: Chen X 

PROVIDER: S-EPMC8526201 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature