Exploring Missense Mutations in Tyrosine Kinases Implicated with Neurodegeneration

Mol Neurobiol. 2017 Sep;54(7):5085-5106. doi: 10.1007/s12035-016-0046-5. Epub 2016 Aug 20.

Abstract

Protein kinases are one of the largest families of evolutionarily related proteins and the third most common protein class of human genome. All the protein kinases share the same structural organization. They are made up of an extracellular domain, transmembrane domain and an intra cellular kinase domain. Missense mutations in these kinases have been studied extensively and correlated with various neurological disorders. Individual mutations in the kinase domain affect the functions of protein. The enhanced or reduced expression of protein leads to hyperactivation or inactivation of the signalling pathways, resulting in neurodegeneration. Here, we present extensive analyses of missense mutations in the tyrosine kinase focussing on the neurodegenerative diseases encompassing structure function relationship. This is envisaged to enhance our understanding about the neurodegeneration and possible therapeutic measures.

Keywords: ALK; ErbB3; Missense mutations; MuSK; NTRK1; Neurodegenerative diseases; PANK2; Protein kinases; Tyrosine kinases.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Mutation, Missense / genetics*
  • Neurodegenerative Diseases / genetics*
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Signal Transduction / genetics

Substances

  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases