Angiotensin-Converting Enzyme as a Potential Target for Treatment of Alzheimer's Disease: Inhibition or Activation?

作者：Zou Kun^*; Michikawa Makoto

来源：Reviews in the Neurosciences, 2008, 19(4-5): 203-212.

• angiotensin-converting enzyme (ACE)
• Alzheimer's disease
• amyloid beta-protein (A beta)
• A beta deposition
• A beta degradation
• ACE inhibitor

The accumulation of the amyloid P-protein (A beta), the main constituent of the 'amyloid plaque', is widely considered to be the key pathological event in Alzheimer's disease (AD). In particular, the accumulation of A beta(42) is the central event triggering neurodegeneration. Reduction of A beta is now a major therapeutic strategy. However, only a few patients show evidence of increased AP production. Thus, defects in proteases that degrade AP could underlie some or many cases of familial and sporadic AD. Among the A beta degrading enzymes, namely, neprilysin (NEP), insulin-degrading enzyme (IDE), endothelin-converting enzyme (ECE) and angiotensin-converting enzyme (ACE), ACE is the most commonly targeted enzyme by inhibitors in elderly populations because it plays a central role in the regulation of blood pressure and hypertension. Genetic, pathological and biochemical studies have associated ACE with AD. This review discusses genetic, molecular and clinical studies that might help explain the relationship between ACE, hypertension, AP degradation and AD.

• 出版日期2008