Proteolytic degradation of the amyloid beta-protein: the forgotten side of Alzheimer's disease.
Proteases have long played a central role in the molecular pathogenesis of Alzheimer's disease (AD), yet proteases that degrade the amyloid beta-protein (Abeta) itself were largely ignored until only quite recently. Today, we know that Abeta-degrading proteases are critical regulators of brain Abeta levels in vivo, with evidence accumulating that their dysfunction may play a role in the etiology of AD. This review explores the historical factors that obscured this important aspect of amyloidogenesis, and discusses the many fresh insights it offers into the causes of and potential treatments for AD.
Leissring
Malcolm A
MA
Department of Biochemistry, The Scripps Research Institute, Scripps Florida, 5353 Parkside Dr., RE-2, Jupiter, FL 33458, USA. Leissring@scripps.edu
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D010447:Peptide Hydrolases