Pin1: a therapeutic target in Alzheimer neurodegeneration

J Mol Neurosci. 2002 Dec;19(3):275-87. doi: 10.1385/JMN:19:3:275.

Abstract

In Alzheimer's disease, the peptidyl prolyl cis/trans isomerase Pin1 binds to phospho-Thr231 on Tau proteins and, hence, is found within degenerating neurons, where it is associated to the large amounts of abnormally phosphorylated Tau proteins. Conversely, Pin1 may restore the tubulin polymerization function of these hyperphosphorylated Tau. In the present work, we investigated, both at the cellular and molecular levels, the role of Pin1 in Alzheimer's disease through the study of its interactions with phosphorylated Tau proteins. We also showed that in neuronal cells, Pin1 upregulates the expression of cyclin D1. This, in turn, could facilitate the transition from quiescence to the G1 phase (re-entry in cell cycle) in a neuron and, subsequently, neuronal dedifferentiation and apoptosis. The involvement of Pin1 in the G0/G1 transition in neurons points to its function as a good target for the development of new therapeutic strategies in neurodegenerative disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism*
  • Cell Line
  • Cyclin D1 / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Naphthoquinones / pharmacology
  • Neuroblastoma / metabolism
  • Neurons / enzymology*
  • Neurons / pathology
  • Peptidylprolyl Isomerase / antagonists & inhibitors
  • Peptidylprolyl Isomerase / chemistry*
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Phosphopyruvate Hydratase / metabolism
  • Phosphorylation
  • Protein Binding / physiology
  • Protein Structure, Tertiary / physiology
  • Spectrometry, Fluorescence
  • tau Proteins / chemistry
  • tau Proteins / metabolism

Substances

  • NIMA-Interacting Peptidylprolyl Isomerase
  • Naphthoquinones
  • tau Proteins
  • Cyclin D1
  • Phosphopyruvate Hydratase
  • PIN1 protein, human
  • Peptidylprolyl Isomerase
  • juglone