title: Special Issue on "Cdk5 and Brain Disorders": Prologue.
abstract: Cyclin-dependent kinase 5 (Cdk5) was identified almost two decades ago as a Tau kinase specific to the nervous system. Shortly after its discovery, it was revealed that this atypical member of the CDK family does not partner with cyclins but with two other proteins, p35 and p39. P35 is predominantly expressed in post-mitotic neurons, whereas p39 is expressed in many different tissues including the brain, pancreas, muscle cells, neutrophils, and many other cell types. A proline-directed serine/threonine (S/T) kinase, predominantly active in the nervous system, Cdk5 regulates a multitude of functions including nervous system development, neuronal migration, cytoskeletal dynamics, axonal guidance, synaptic plasticity, neurotransmission, neuronal survival and death, to mention a few. In association with its ubiquitous expression in other tissues, Cdk5 is implicated in a wide range of functions, such as gene transcription, vesicular transport, apoptosis, cell adhesion, migration, exocytosis, etc. A focal point of investigation surrounding Cdk5 is its deregulation in pathogenic processes of neurodegenerative disorders, which has emphasized on its hyperactivation by p25, a calpain-cleaved product of p35 leading to Tau and neurofilament hyperphosphorylation followed by neuronal death. What has intrigued researchers about Cdk5 is its tight regulation in carrying out many normal physiological functions while its deregulation under pathological conditions, is linked to neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Neiman Pick's Type C disease and others. Between these two so-called 'good Cdk5 (Cdk5/p35)' and 'bad Cdk5 (Cdk5/p25)', the latter has become the target for therapeutic intervention in neurodegenerative disorders.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, USA.
authors.forename: Jyotshnabala
authors.initials: J
authors.lastname: Kanungo