Cdk5: multitasking between physiological and pathological conditions.

摘要: Abstract Cyclin-dependent kinase 5 (Cdk5) is a peculiar proline-directed serine/threonine kinase. Unlike the other members of Cdk family, Cdk5 not directly involved in cell cycle regulation, being normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity. This present mainly post-mitotic neurons its activity tightly regulated by interaction specific activators, p35 p39. Despite pivotal role CNS development, dysregulation has been implicated different pathologies, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's (PD) and, most recently, prion-related encephalopathies (PRE). In these neurodegenerative conditions, overactivation relocalization occurs upon association p25, truncated form normal activator p35. switching will cause shift phosphorylative pattern Cdk5, an alteration both targets activity, ultimately leading to demise. AD PRE, two disorders that share clinical neuropathological features, linking event between major markers: amyloid plaques, tau hyperphosphorylation loss. Moreover, this was shown be abortive re-entry, feature recently proposed possible step apoptosis mechanism several neurological diseases. review focuses on neurons, namely regulation cytoskeletal dynamics, function survival, physiological pathological highlighting relevance main mechanisms neurodegeneration brain pathologies.