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Abstract
Grant Number: 1R03DA024890-01 Project Title: Discovering Calpain Inhibitors for Neurological Diseases
PI Information: Name Title GLASS, JONATHAN DAVID. jglas03@emory.edu ASSOCIATE PROFESSOR Abstract: DESCRIPTION (provided by applicant): Calpain inhibitors have enormous potential as therapeutic agents for neurological diseases. Calpains are calcium-activated cysteine proteases that are major contributors to the process of axonal and neuronal degeneration. Degeneration of axons leads to the disconnection of neurons from their motor or sensory targets, leading to weakness, numbness, pain, and cognitive impairment. Axonal degeneration underlies neurological dysfunction in stroke, head and spinal cord injury, peripheral neuropathies, and multiple sclerosis. We have had success in preventing axonal degeneration and neurological dysfunction in a model of peripheral neuropathy. We propose to use the Molecular Libraries Screening Center at Emory University for high throughput screening of a large library of small molecules (up to 100,000) for calpain inhibitor activity. We have developed a secondary assay for independent analysis of "hits", and plan for follow-up developmental chemistry for optimizine drug design. Thus, the resources of the MLSCN will allow us to identify new calpain inhibitor compounds that may provide important new treatment for patients with a variety of neurological diseases. The degeneration of axons is a pathological feature common to many neurological diseases that causes neurological disability due to disconnection of neurons from their targets. Preventing axonal degeneration is thus protective, and we are proposing to discover small molecules that can be used for this purpose. The target of our small molecule screen is the calcium-activated protease calpain. Inhibitors of calpain will be developed as novel treatments of neurological diseases.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
calpain, drug design /synthesis /production, enzyme inhibitor, high throughput technology, neuropharmacologic agent, small molecule
NIH Roadmap Initiative tag
Institution: EMORY UNIVERSITY 1599 CLIFTON ROAD, 4TH FLOOR ATLANTA, GA 30322 Fiscal Year: 2007 Department: NEUROLOGY Project Start: 01-SEP-2007 Project End: 31-AUG-2009 ICD: NATIONAL INSTITUTE ON DRUG ABUSE IRG: ZMH1