Kinases in synaptic development and neurological diseases

Abstract

Neuronal morphogenesis and synapse development is essential for building a functioning nervous system, and defects in these processes are associated with neurological disorders. Our understanding of molecular components and signalling events that contribute to neuronal development and pathogenesis is limited. Genes associated with neurodevelopmental and neurodegenerative diseases provide entry points for elucidating molecular events that contribute to these conditions. Several protein kinases, enzymes that regulate protein function by phosphorylating their substrates, are genetically linked to neurological disorders. Identifying substrates of these kinases is key to discovering their function and providing insight for possible therapies. In this review, we describe how various methods for kinase-substrate identification helped elucidate kinase signalling pathways important for neuronal development and function. We describe recent advances on roles of kinases TAOK2, TNIK and CDKL5 in neuronal development and the converging pathways of LRRK2, PINK1 and GAK in Parkinson's Disease.