Dual vulnerability of TDP-43 to calpain and caspase-3 proteolysis after neurotoxic conditions and traumatic brain injury.

ABSTRACT: Transactivation response DNA-binding protein 43 (TDP-43) proteinopathy has recently been reported in chronic traumatic encephalopathy, a neurodegenerative condition linked to prior history of traumatic brain injury (TBI). While TDP-43 appears to be vulnerable to proteolytic modifications under neurodegenerative conditions, the mechanism underlying the contribution of TDP-43 to the pathogenesis of TBI remains unknown. In this study, we first mapped out the calpain or caspase-3 TDP-43 fragmentation patterns by in vitro protease digestion. Concurrently, in cultured cerebrocortical neurons subjected to cell death challenges, we identified distinct TDP-43 breakdown products (BDPs) of 35, 33, and 12 kDa that were indicative of dual calpain/caspase attack. Cerebrocortical culture incubated with c

SUBMITTER: Yang Z 

PROVIDER: S-EPMC4158661 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature