PROTECTIVE EFFECTS OF Α - CRYSTALLIN ON Β - AMYLOID (Aβ) INDUCED TOXICITY

Abstract

Objectives: To investigate the protective role of α-crystallin against β-amyloid aggregation.

Methods: In vitro spectroscopic methods and cell culture studies were done to validate our objective.

Results: The molecular basis of alzhemiers disease has been proposed to be accumulation and aggregation of β-amyloid (Aβ). However, prevention of β-amyloid aggregation is still a promising means to reduce its neurotoxicity. In this work, we show that α-crystallin was able to inhibit cellular toxicity of Aβ on astrocytes and lymphocytes. Theα−crystallin (αA and αB): the two vertebrate eye lens proteins that are related to the small heat shock protein family, was able to reverse the oxidative stress induced by Aβ1-42. Treatment of α-crystallin enhances the activity of proteasome and it also induces the expression of Hsp70 which is known to inhibit the intramolecular misfolding. We also demonstrate that Aβ1-42 suppresses the expression of TriC chaperonin subunits TCPβ and TCPε, which are known to play a role in folding of misfolded proteins.α-crystallin reverses this effect and enhances the expression of TCPβ and TCPε.

Conclusions: Research findings in this study provide the basis for the development of novel pharmacotherapy for Alzhemier's disease.