New Prospects and Strategies for Drug Target Discovery in Neurodegenerative Disorders

• Published in: NeuroRx Vol. 2; no. 4; pp. 627 - 637
• Main Authors: Hilbush, Brian S., Morrison, John H., Young, Warren G., Sutcliffe, J. Gregor, Bloom, Floyd E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2005; Springer Nature B.V; The American Society for Experimental NeuroTherapeutics, Inc
• Subjects: Alzheimer's; Animals; Central Nervous System Agents - therapeutic use; Drug Design; genes; genomics; Humans; Medical research; Neurodegeneration; Neurodegenerative Diseases - drug therapy; Neurodegenerative Diseases - physiopathology; QTL; Review; therapeutics; QTL; genomics; therapeutics; Neurodegeneration; genes; Alzheimer's
• ISSN: 1545-5343; 1933-7213; 1545-5351; 1878-7479
• DOI: 10.1602/neurorx.2.4.627

The future of neurodegenerative therapeutics development depends upon effective disease modification strategies centered on carefully investigated targets. Pharmaceutical research endeavors that probe for a much deeper understanding of disease pathogenesis, and explain how adaptive or compensatory mechanisms might be engaged to delay disease onset or progression, will produce the needed breakthroughs. Below, we discuss the prospects for new targets emerging out of the study of brain disease genes and their associated pathogenic pathways. We describe a general experimental paradigm that we are employing across several mouse models of neurodegenerative disease to elucidate molecular determinants of selective neuronal vulnerability. We outline key elements of our target discovery program and provide examples of how we integrate genomic technologies, neuroanatomical methods, and mouse genetics in the search for neurodegenerative disease targets.