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

• Published in: Journal of neuroscience research Vol. 86; no. 6; pp. 1343 - 1352
• Main Authors: Björkdahl, Cecilia, Sjögren, Magnus J., Zhou, Xinwen, Concha, Hernan, Avila, Jesus, Winblad, Bengt, Pei, Jin-Jing
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2008
• Subjects: Alzheimer's disease; heat shock proteins; kinases; phosphorylation; tau
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.21589

The heat‐shock proteins (HSPs) Hsp27 and αB‐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 αB‐crystallin in AD brain samples were significantly increased (by ∼20% and ∼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 αB‐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 αB‐crystallin resulted in decreased levels of phosphorylated tau, NF, and GSK‐3β. It was also shown that overexpression of HSPs causes an increase in the percentage of cells present in the G1 phase. The results presented suggest that a cellular defense against dysregulated proteins, in the form of Hsp27 and αB‐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. © 2007 Wiley‐Liss, Inc.