Role of UCHL1 in axonal injury and functional recovery after cerebral ischemia.

ABSTRACT: Ubiquitin C-terminal hydrolase L1 (UCHL1) is a unique brain-specific deubiquitinating enzyme. Mutations in and aberrant function of UCHL1 have been linked to many neurological disorders. UCHL1 activity protects neurons from hypoxic injury, and binding of stroke-induced reactive lipid species to the cysteine 152 (C152) of UCHL1 unfolds the protein and disrupts its function. To investigate the role of UCHL1 and its adduction by reactive lipids in inhibiting repair and recovery of function following ischemic injury, a knock-in (KI) mouse expressing the UCHL1 C152A mutation was generated. Neurons derived from KI mice had less cell death and neurite injury after hypoxia. UCHL1 C152A KI and WT mice underwent middle cerebral artery occlusion (MCAO) or sham surgery. White matter injury was signifi

SUBMITTER: Liu H 

PROVIDER: S-EPMC6410860 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature