Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging
| Autor: | Kundan Malik, Lindsay Brown, Shin Murakami, Duc Le |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
hypertension QH301-705.5 Review Peptidyl-Dipeptidase A Catalysis Inorganic Chemistry angiotensin-converting enzyme amyloid-degrading enzyme Internal medicine Alzheimer’ s disease medicine Dementia Animals Humans Genetic Predisposition to Disease age-related comorbidities Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy stress resistance Amyloid beta-Peptides biology business.industry Organic Chemistry aging Genetic Variation Angiotensin-converting enzyme General Medicine life extension Stress resistance medicine.disease Computer Science Applications Disease Models Animal Chemistry Endocrinology cardiology biology.protein business dementia |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 13178, p 13178 (2021) International Journal of Molecular Sciences |
| ISSN: | 1661-6596 1422-0067 |
| DOI: | 10.0197/v1 |
| Popis: | A 2018 report from the American Heart Association shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin–angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, and heart failure, among others. It has been suggested that ACE inhibitors can alleviate the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that genetic variants of the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases, while other variants are associated with reduced risk of AD. In mice, ACE overexpression in the brain reduces symptoms of the AD model systems. Thus, we find two opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin–angiotensin system; (2) amyloid-degrading enzyme that hydrolyzes beta-amyloid, reducing amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to AD to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during midlife, leading to age-related later events. |
| Databáze: | OpenAIRE |
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