PROTECTIVE EFFECTS OF Î‘ - CRYSTALLIN ON Î’ - AMYLOID (AÎ²) INDUCED TOXICITY
Objectives: To investigate the protective role of Î±-crystallin against Î²-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 Î²-amyloid (AÎ²). However, prevention of Î²-amyloid aggregation is still a promising means to reduce its neurotoxicity. In this work, we show that Î±-crystallin was able to inhibit cellular toxicity of AÎ² on astrocytes and lymphocytes. TheÎ±âˆ’crystallin (Î±A and Î±B): 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 AÎ²1-42. Treatment of Î±-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 AÎ²1-42 suppresses the expression of TriC chaperonin subunits TCPÎ² and TCPÎµ, which are known to play a role in folding of misfolded proteins.Î±-crystallin reverses this effect and enhances the expression of TCPÎ² and TCPÎµ.
Conclusions: Research findings in this study provide the basis for the development of novel pharmacotherapy for Alzhemier's disease.