Dementia Japan30:174-183, 2016

Regulation of α-secretase activity in Alzheimer's disease

Mikiko Ohno, Eiichiro Nishi

Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University

Deposition of amyloid β peptide (Aβ) is one of the pathological hallmarks of Alzheimer's disease (AD).  Aβ is produced by the sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretase.  As α-secretase cleavage occurs within the Aβ domain, it has the potential to preclude the generation of Aβ.  Several lines of evidences demonstrated that the major α-secretase appears to be ADAM10.  Overexpression of ADAM10 in the AD mouse model reduced Aβ deposition, indicating that activation of α-secretase is beneficial for the prevention of AD.  Acitretin, a potential inducer of ADAM10 expression, is a candidate for an activator of α-secretase.  We demonstrate here that nardilysin, a multi-functional metalloprotease, is a critical regulator for α-secretase activity.

Address correspondence to Dr. Eiichi Nishi, Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University (54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto City, Kyoto 606-8507, Japan)