Small heat shock proteins Hsp27 or alphaB-crystallin and the protein components of neurofibrillary tangles: tau and neurofilaments

Cecilia Björkdahl, Magnus J Sjögren, Xinwen Zhou, Hernan Concha, Jesus Avila, Bengt Winblad, Jin-Jing Pei

69 Citations (Scopus)

Abstract

The heat-shock proteins (HSPs) Hsp27 and alphaB-crystallin are up-regulated in Alzheimer's disease (AD), but the extent of this and the consequences are still largely unknown. The HSPs are involved in protein degradation and protection against protein aggregation, and they interact with several cytoskeletal components such as microtubules (MT) and neurofilaments (NF). AD pathology includes aggregated proteins (tau, NF), decreased protein degradation, and cytoskeletal disruption. It is thus of interest to investigate more closely the possible roles of the HSPs in AD pathology. The expressions of Hsp27 and alphaB-crystallin in AD brain samples were significantly increased (by approximately 20% and approximately 30%, respectively) and correlated significantly with phosphorylated tau and NF proteins. To investigate the consequences of increased HSP levels on tau and NF regulation, N2a cells were transfected with Hsp27 or alphaB-crystallin constructs, and overexpression of the HSPs was confirmed in the cells. Increased tau phosphorylation at the Ser262 site in the N2a cells was regulated by Hsp27 overexpression (possibly through p70S6k), whereas the overexpression of alphaB-crystallin resulted in decreased levels of phosphorylated tau, NF, and GSK-3beta. It was also shown that overexpression of HSPs causes an increase in the percentage of cells present in the G(1) phase. The results presented suggest that a cellular defense against dysregulated proteins, in the form of Hsp27 and alphaB-crystallin, might contribute to the cell cycle reentry seen in AD cells. Furthermore, Hsp27 might also be involved in AD pathology by aggravating MT disruption by tau phosphorylation.

Original languageEnglish
JournalJournal of Neuroscience Research
Volume86
Issue number6
Pages (from-to)1343-52
Number of pages10
ISSN0360-4012
DOIs
Publication statusPublished - 1 May 2008
Externally publishedYes

Keywords

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease
  • Animals
  • Blotting, Western
  • Brain
  • Cell Cycle
  • Cell Line, Tumor
  • Female
  • Flow Cytometry
  • Glycogen Synthase Kinase 3
  • HSP27 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Humans
  • Immunoblotting
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Proteins
  • Neurofibrillary Tangles
  • Neurofilament Proteins
  • Phosphorylation
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Transfection
  • alpha-Crystallin B Chain
  • tau Proteins
  • Journal Article
  • Research Support, Non-U.S. Gov't

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