Linking microtubules to Parkinson's disease: the case of parkin

Biochem Soc Trans. 2015 Apr;43(2):292-6. doi: 10.1042/BST20150007.

Abstract

Microtubules (MTs) are dynamic polymers consisting of α/β tubulin dimers and playing a plethora of roles in eukaryotic cells. Looking at neurons, they are key determinants of neuronal polarity, axonal transport and synaptic plasticity. The concept that MT dysfunction can participate in, and perhaps lead to, Parkinson's disease (PD) progression has been suggested by studies using toxin-based and genetic experimental models of the disease. Here, we first learn lessons from MPTP and rotenone as well as from the PD related genes, including SNCA and LRRK2, and then look at old and new evidence regarding the interplay between parkin and MTs. Data from experimental models and human cells point out that parkin regulates MT stability and strengthen the link between MTs and PD paving the way to a viable strategy for the management of the disease.

Publication types

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

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / administration & dosage
  • Animals
  • Disease Models, Animal
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Mice
  • Microtubules / drug effects
  • Microtubules / genetics*
  • Microtubules / pathology
  • Mutation
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / drug therapy
  • Parkinson Disease, Secondary / genetics*
  • Parkinson Disease, Secondary / pathology
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Rotenone / administration & dosage
  • Tubulin / genetics
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism

Substances

  • SNCA protein, human
  • Tubulin
  • alpha-Synuclein
  • Rotenone
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Ubiquitin-Protein Ligases
  • parkin protein
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein-Serine-Threonine Kinases