The Immediate Early Gene Arc Interacts with Endocytic Machinery and Regulates the Trafficking and Function of Presenilin

Abstract (Set) These discoveries promise a novel approach to develop agents to regulate presenilin 1 (PS 1) and treat Alzheimer's Disease and age-dependent memory decline. PS 1 functions as part of the gamma secretase (protease) complex that acts on amyloid precursor protein (APP), Notch and several other transmembrane proteins. Familial Alzheimer's disease results from mutations of PS 1. Recent studies indicate that gamma secretase activity is blocked by agents that interrupt endocytosis. This observation indicates that agents that selectively regulate PS 1 endocytosis can regulate its activity. JHU scientists have discovered that the novel immediate early gene, termed Arc, directly interacts with PS 1 (and endocytosis proteins) and induces PS 1 to accumulate in endosomes where it co-localizes with Arc, other components of the gamma secretase complex and APP. A small peptide sequence in Arc has been identified that is necessary and sufficient to mediate the interaction. JHU scientists have also developed tools for high throughput screens that can identify agents that selectively regulate the interaction. Description (Set) Proposed Use (Set) Agents that modify the regulatory effects of Arc on PS 1 can be anticipated to be useful to treat Alzheimer's Disease, as well as age-related memory decline.

Inventor(s): Worley, Paul F. ,Chowdhury, Shoaib,Shepherd, Jason

Type of Offer: Licensing

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