Title:ACAT1 as a Therapeutic Target and its Genetic Relationship with Alzheimer's Disease
Volume: 16
Issue: 8
关键词:
阿尔茨海默氏病，胆固醇代谢，胆固醇酯，抑制ACAT1，药物遗传学，治疗靶标。
摘要:
Background: Alzheimer´s disease (AD) is a chronic and progressive disease which impacts
caregivers, families and societies physically, psychologically and economically. Currently available
drugs can only improve cognitive symptoms, have no impact on progression and are not curative, so
identifying and studying new drug targets is important. There are evidences which indicate disturbances
in cholesterol homeostasis can be related with AD pathology, especially the compartmentation of intracellular
cholesterol and cytoplasmic cholesterol esters formed by acyl-CoA: cholesterol acyltransferase
1 (ACAT1) can be implicated in the regulation of amyloid-beta (Aβ) peptide, involved in AD. Blocking
ACAT1 activity, beneficial effects are obtained, so it has been suggested that ACAT1 can be a potential
new therapeutic target. The present review discusses the role of cholesterol homeostasis in AD pathology,
especially with ACAT inhibitors, and how they have been raised as a therapeutic approach. In addition,
the genetic relationship of ACAT and AD is discussed.
Conclusion: Although there are several lines of evidence from cell-based and animal studies that suggest
that ACAT inhibition is an effective way of reducing cerebral Aβ, there is still an information gap
in terms of mechanisms and concerns to cover before passing to the next level. Additionally, an area of
interest that may be useful in understanding AD to subsequently propose new therapeutic approaches is
pharmacogenetics; however, there is still a lot of missing information in this area.
