Affordable Access

Publisher Website

Novel therapeutic strategies for neurodegenerative disease.

Authors
  • 1
Type
Published Article
Journal
Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society
1479-8301
Publication Date
Volume
9
Issue
2
Pages
103–109
Identifiers
DOI: 10.1111/j.1479-8301.2009.00289.x
PMID: 19604333
Source
Medline

Abstract

The activity of protein phosphatase 2A (PP2A) is compromised and believed to be the cause of the abnormal hyperphosphorylation of tau in Alzheimer's disease (AD) brain. Activity of PP2A is regulated by two endogeneous inhibitor proteins, called as I(1)(PP2A) and I(2)(PP2A). Previously, we reported that: (i) I(1)(PP2A) and I(2)(PP2A) are upregulated with cleavage of I(2)(PP2A) holoprotein and translocation of its amino terminal fragment from the nucleus to the cytoplasm in neuronal cells in AD brains; and (ii) translocated I(2)(PP2A) colocalized not only with the PP2A catalytic subunit, but also with phosphorylated tau in neuronal cytoplasm. Furthermore, according to preliminary data, the cleavage site of I(2)(PP2A) is located between amino acids 175 and 176 of the I(2)(PP2A) sequence. Because the sequence from amino acids 168 to 181 on I(2)(PP2A) presumably functions as a nuclear localization signal (NLS), inhibition of break down of the NLS in I(2)(PP2A) is expected to be a novel therapeutic target for the treatment of Alzheimer's disease.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments
F