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The brain RAS and Alzheimer's disease
John W Wright1, Joseph W Harding
1Departments of Psychology, Veterinary and Comparative, Anatomy, Pharmacology and Physiology, and Programs in Neuroscience and Biotechnology, Washington State University, Pullman, Pullman, WA 99164-4820, USA. wrightjw@wsu.edu
Experimental Neurology
|September 29, 2009
Summary
This review explores the brain renin-angiotensin system (RAS) and its role in Alzheimer's disease (AD). New angiotensin IV analogue drugs show promise for treating cognitive impairment by enhancing memory in animal models.
Area of Science:
- Neuroscience
- Pharmacology
- Gerontology
Background:
- Alzheimer's disease (AD) presents a growing global health challenge, with increasing dementia rates linked to rising life expectancy.
- Middle-adulthood hypertension is a significant risk factor for later-life cognitive impairment.
- Antihypertensive drugs like ACE inhibitors and ARBs may slow AD progression, but ACE inhibitors might increase amyloid-beta accumulation.
Purpose of the Study:
- To review the brain renin-angiotensin system (RAS) and the efficacy of ACE inhibitors in treating dementia.
- To explore the AT(4) receptor and its agonists as potential therapeutic targets for AD-associated memory deficits.
- To describe the development of novel, blood-brain barrier-penetrant angiotensin IV analogues for cognitive enhancement.
Main Methods:
- Literature review of the brain renin-angiotensin system (RAS) and antihypertensive drug efficacy in AD.
- Examination of the AT(4) receptor and its potential as a therapeutic target.
- Development and preclinical testing of blood-brain barrier-penetrant angiotensin IV analogues in AD animal models.
Main Results:
- ACE inhibitors show potential in reducing AD likelihood and progression, but may increase amyloid-beta (Aβ) accumulation.
- The AT(4) receptor presents a novel target for managing memory impairments in AD.
- Developed angiotensin IV analogues demonstrate favorable hydrophobicity and memory-facilitating effects in animal models of AD.
Conclusions:
- The brain RAS is a critical factor in AD pathogenesis and treatment.
- Targeting the AT(4) receptor offers a promising new therapeutic avenue for AD.
- Novel angiotensin IV analogues represent a potential breakthrough for treating AD-related cognitive decline.
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