Small heat shock proteins differentially affect Abeta aggregation and toxicity.
beta-Amyloid (Abeta) is the primary protein component of senile plaques in Alzheimer's disease (AD) and has been implicated in neurotoxicity associated with the disease. Abeta aggregates readily in vitro and in vivo, and its toxicity has been linked to its aggregation state. Prevention of Abeta aggregation has been investigated as a means to prevent Abeta toxicity associated with AD. Recently we found that Hsp20 from Babesia bovis prevented both Abeta aggregation and toxicity [S. Lee, K. Carson, A. Rice-Ficht, T. Good, Hsp20, a novel alpha-crystallin, prevents Abeta fibril formation and toxicity, Protein Sci. 14 (2005) 593-601.]. In this work, we examined the mechanism of Hsp20 interaction with Abeta1-40 and compared its activity to that of other small heat shock proteins, carrot Hsp17.7 and human Hsp27. While all three small heat shock proteins were able to prevent Abeta aggregation, only Hsp20 was able to attenuate Abeta toxicity in cultured SH-SY5Y cells. Understanding the mechanism of the Hsp20-Abeta interaction may provide insights into the design of the next generation of Abeta aggregation and toxicity inhibitors.
Lee
Sungmun
S
Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, USA.
Carson
Kenneth
K
Rice-Ficht
Allison
A
Good
Theresa
T
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D050886:HSP20 Heat-Shock Proteins / Q000737:chemistry / Q000494:pharmacology / Q000648:ultrastructure; D050888:Heat-Shock Proteins, Small / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology / Q000648:ultrastructure; D011487:Protein Conformation / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D016229:Amyloid beta-Peptides; D050886:HSP20 Heat-Shock Proteins; D050888:Heat-Shock Proteins, Small; D010446:Peptide Fragments; D011994:Recombinant Proteins; C078592:amyloid beta-protein (1-40)