Brain Disorders & Therapy

Abstract

Septin Phosphorylation and Neuronal Degeneration; Role of Cyclin Dependent Kinase 5 (Cdk5)

Niranjana D Amin, Philip Grant, Yali Zheng, Sashi Kesavapany and Harish C Pant

It is evident from the literature that most cellular functions are mediated by protein phosphorylation. It has also been demonstrated that abnormal phosphorylation of neuronal cytoskeletal proteins often leads to the pathology of several neurodegenerative diseases. For example, hyperphosphorylation of microtubule associated tau protein by Cdk5 and other kinases such as GSK3 has been linked to the formation of neurofibrillary tangles (NFTs) associated with Alzheimer’s disease (AD). Septins, a family of cytoskeletal proteins, also expressed in mammalian neurons, are involved in synaptic function and have also been linked to various neurological disorders. Although Sept5 phosphorylation by Cdk5 at the synapse has been reported to modulate exocytotic function, as yet, its phosphorylation has not been linked to hyperactivated Cdk5 as seen in AD. The present review begins with an overview of Cdk5 function in the nervous system, its role in neurodegeneration and its relationship to neuronal septins, their function and role in neurological disorders. In a summary speculation, we attempt to correlate synaptic function of Cdk5 phosphorylation of septins that may play a role in the etiology of neuronal disorders.