Innovative genetic approach uncovers target of promising molecule ISRIB
ISRIB, a drug-like molecule that inhibits the integrated stress response, was identified in 2013 in Peter Walter’s lab at UCSF. The integrated stress response is a central pathway in mammalian proteostasis, disruptions to which are believed to be central in many neurodegenerative diseases. When given to mice, ISRIB enhanced memory and learning. In collaboration with the Walter lab, IND faculty Martin Kampmann utilized a functional genomics approach to discover the target of ISRIB. The action of ISRIB depends on eIF2B, a nucleotide exchange factor important for protein production. The team then confirmed that the delta subunit of elF2B is the direct target of ISRIB. This molecular understanding might enable the development of ISRIB into a drug for the treatment of human neurologic diseases.
The study was published in the April 15, 2015... Read more ...