Vladimir F Lazarev
Institute of Cytology (RAS), Russia
Title: A low molecular weight GAPDH binder reduces secondary damage after traumatic brain injury on rats
Biography
Biography: Vladimir F Lazarev
Abstract
Extensive death of neurons can be caused by neurodegenerative pathologies or massive cell damage due to ischemia or traumatic brain injure (TBI). Such pathological conditions lead to the emergence of various proteins in the intercellular space. These proteins can regulate the development of secondary damage due to a clearly expressed toxic effect on the surrounding cells. In this work, we demonstrated the possibility of inhibiting the cytotoxic effect of such aggregates by treatment with specific drug that bind the GAPDH protein, a well-known participant of aggregation, in the intercellular space. Selected chemical – hydrocortisone derivative RX624 prevented the interaction of exogenous GAPDH with cell membrane and reduced the death of the acceptor cells. We also demonstrated efficiency of RX624 treatment on rat model of TBI. This chemical blocked formation of GAPDH aggregates, inhibited cytotoxic effects of cerebrospinal fluid and rescue motor function of injured rats. Importantly, that RX624 treatment of rats had the similar effect with specific anti-GAPDH antibodies intracranial injection.