Effect of angiotensin II type 2 receptor on stroke, cognitive impairment and neurodegenerative diseases

Area of Science:

• Neuroscience
• Pharmacology
• Cardiovascular Research

Background:

• The renin-angiotensin system (RAS) is implicated in cognitive function and neurodegenerative diseases.
• Angiotensin II signaling through AT(1) receptors exacerbates ischemic brain damage, while AT(2) receptor signaling demonstrates protective effects.

Purpose of the Study:

• To review the role of RAS in cognitive impairment and neurodegenerative disease.
• To discuss experimental studies on the angiotensin II type 2 (AT(2)) receptor's function in the brain.
• To explore the therapeutic potential of RAS modulation for neurological disorders.

Main Methods:

• Review of experimental studies on RAS components, particularly the AT(2) receptor.
• Investigation of ischemic brain damage in mouse models with manipulated RAS activity.
• Administration of a novel AT(2) receptor agonist (Compound 21) to assess cognitive function in mice.
• Analysis of RAS component levels in cerebrospinal fluid of patients with neurodegenerative diseases.

Main Results:

• Overexpression of angiotensin II worsens ischemic brain damage, increasing oxidative stress.
• AT(2) receptor signaling, especially in hematopoietic cells, protects against ischemic brain injury.
• Direct AT(2) receptor stimulation with Compound 21 enhanced cognitive function in wild-type and Alzheimer's disease mouse models.
• Patients with multiple sclerosis showed reduced angiotensin II and ACE2, and increased ACE levels in cerebrospinal fluid.

Conclusions:

• RAS is significantly involved in both ischemic brain damage and cognitive function.
• AT(2) receptor activation offers neuroprotection and cognitive enhancement.
• RAS component alterations in cerebrospinal fluid suggest its role in neurodegenerative diseases like multiple sclerosis.
• Modulating the RAS presents a potential therapeutic strategy for protecting neurons in various neurological conditions.