Vascular Dementia

Biography

Harish C Pant supervises and manages a research program dedicated to understanding the mechanisms regulating neuronal cytoskeletal phosphorylation in health and disease. For several years our focus has been on the role of the multifunctional neuronal kinase complex Cdk5/p35, in neuronal cytoskeleton phosphorylation, neuronal development, synapogenesis, and survival. Within the past few years, however, we, and other laboratories, have shown that Cdk5 is abnormally hyperactivated as a Cdk5/p25 complex in several neurodegenerative disorders which correlates with their specific brain pathologies. Serendipitously, we identified a small peptide (p5) derived from the cdk5 activator, p35, that specifically inhibited the abnormally activated Cdk5 without affecting the normal endogenous kinase. Accordingly, current and future studies are designed to (1) determine whether this peptide acts therapeutically in rescuing neurodegenerative model mice sharing the hyperactivated Cdk5-induced phenotypes of Alzheimer Disease (AD), Amyotrophic Sclerosis (ALS), Parkinson’s disease (PD) and HIV-dementia. (2) if so, what is its mechanism of action in each case? And, ultimately, (3) does it qualify as a possible candidate for human therapy?

Research Interest

The major focus of this laboratory has been to study the mechanisms of topographic regulation of neuronal cytoskeletal proteins regulation by phosphorylation and neurodegeneration.