Presenilin 1 deficiency impairs Aβ42-to-Aβ40- and angiotensin-converting activities of ACE

ABSTRACT:

Introduction

Alzheimer’s disease (AD) is associated with amyloid β-protein 1-42 (Aβ42) accumulation in the brain. Aβ42 and Aβ40 are the major two species generated from amyloid precursor protein. We found that angiotensin-converting enzyme (ACE) converts neurotoxic Aβ42 to neuroprotective Aβ40 in an ACE domain– and glycosylation-dependent manner. Presenilin 1 (PS1) mutations account for most of cases of familial AD and lead to an increased Aβ42/40 ratio. However, the mechanism by which PSEN1 mutations induce a higher Aβ42/40 ratio is unclear.

Methods

We over expressed human ACE in mouse wild-type and PS1-deficient fibroblasts. The purified ACE protein was used to analysis the Aβ42-to-Aβ40- and angiotensin-converting activities. The distribution of ACE was determined by Im

SUBMITTER: Gao Y 

PROVIDER: S-EPMC9981673 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature