Pin1 in Alzheimer's disease

D. Allan Butterfield, Hafiz Mohmmad Abdul, Wycliffe Opii, Shelley F. Newman, Gururaj Joshi, Mubeen Ahmad Ansari, Rukhsana Sultana

Research output: Contribution to journalReview articlepeer-review

158 Scopus citations

Abstract

Proteolytic processing and phosphorylation of amyloid precursor protein (APP), and hyperphosphorylation of tau protein, have been shown to be increased in Alzheimer's disease (AD) brains, leading to increased production of β-amyloid (Aβ) peptides and neurofibrillary tangles, respectively. These observations suggest that phosphorylation events are critical to the understanding of the pathogenesis and treatment of this devastating disease. Pin-1, one of the peptidyl-prolyl isomerases (PPIase), catalyzes the isomerization of the peptide bond between pSer/Thr-Pro in proteins, thereby regulating their biological functions which include protein assembly, folding, intracellular transport, intracellular signaling, transcription, cell cycle progression and apoptosis. A number of previous studies have shown that Pin1 is co-localized with phosphorylated tau in AD brain, and shows an inverse relationship to the expression of tau. Pin1 protects neurons under in vitro conditions. Moreover, recent studies demonstrate that APP is a target for Pin1 and thus, in Aβ production. Furthermore, Pin1 was found to be oxidatively modified and to have reduced activity in the hippocampus in mild cognitive impairment (MCI) and AD. Because of the diverse functions of Pin1, and the discovery that this protein is one of the oxidized proteins common to both MCI and AD brain, the question arises as to whether Pin1 is one of the driving forces for the initiation or progression of AD pathogenesis, finally leading to neurodegeneration and neuronal apoptosis. In the present review, we discuss the role of Pin1 with respect to Alzheimer's disease.

Original languageEnglish
Pages (from-to)1697-1706
Number of pages10
JournalJournal of Neurochemistry
Volume98
Issue number6
DOIs
StatePublished - Sep 2006

Keywords

  • Alzheimer's disease
  • Amyloid beta-peptide
  • Apoptosis
  • Cell cycle
  • Cell signaling
  • Hyperphosphorylated tau
  • Peptidyl-prolyl cis/trans isomerases

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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