Paired Ig-like receptor B (PirB): a novel BACE1 substrate in the brain

Project: Research project

Project Details


BACE1 inhibitor drugs are currently being tested in clinical trials for AD. However, BACE1 deficient (BACE1-/-) mice are known to have memory impairment, suggesting BACE1 inhibitors might have mechanism-based toxicities. In order to facilitate therapeutic development of BACE1 inhibitors and avoid potential adverse effects, the role of BACE1 in memory function needs to be elucidated in a timely fashion. We have intriguing preliminary data that PirB, a type I membrane protein that is a negative regulator of synaptic plasticity in the brain, is a novel BACE1 substrate, thus potentially explaining the memory deficits of BACE1-/- mice. We hypothesize that 1) PirB is a BACE1 substrate in neuron and in brain 2) up-regulated PirB in the absence of BACE1 cleavage suppresses synaptic plasticity and causing memory impairment in BACE1-/- mice.
Effective start/end date7/1/156/30/17


  • BrightFocus Foundation (A2015289F)


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