Overexpression of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase A in nerve cells confers resistance to amyloid β and other toxins by decreasing mitochondrial respiration and reactive oxygen species production

Authors

Jordan T. Newington, Western University
Tim Rappon, Western University
Shawn Albers, Robarts Research Institute
Daisy Y. Wong, Robarts Research Institute
R. Jane Rylett, Robarts Research Institute
Robert C. Cumming, Western UniversityFollow

Document Type

Article

Publication Date

10-26-2012

Journal

Journal of Biological Chemistry

Volume

287

Issue

44

First Page

37245

Last Page

37258

URL with Digital Object Identifier

10.1074/jbc.M112.366195

Abstract

Background: Aerobic glycolysis promotes resistance against Aβ toxicity. Results: Increased LDHA and PDK1 expression attenuates mitochondrial activity and confers resistance to Aβ. These proteins are down-regulated in a transgenic Alzheimer disease (AD) mouse model, and PDK1 is decreased in AD brain. Conclusion: PDK and LDHA are central mediators of Aβ resistance. Significance: Drugs that augment aerobic glycolysis may enhance brain cell survival in AD patients. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.