Contributions by the Brain Renin-Angiotensin System to Memory, Cognition, and Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive neuron losses in memory-associated brain structures that rob patients of their dignity and quality of life. Five drugs have been approved by the FDA to treat AD but none modify or significantly slow disease progression. New therapies are needed to delay the course of this disease with the ultimate goal of preventing neuron losses and preserving memory functioning. In this review we describe the renin-angiotensin II (AngII) system (RAS) with specific regard to its deleterious contributions to hypertension, facilitation of neuroinflammation and oxidative stress, reduced cerebral blood flow, tissue remodeling, and disruption of memory consolidation and retrieval. There is evidence that components of the RAS, AngIV and Ang(1-7), are positioned to counter such damaging influences and these systems are detailed with the goal of drawing attention to their importance as drug development targets. Ang(1-7) binds at the Mas receptor, while AngIV binds at the AT4 receptor subtype, and these receptor numbers are significantly decreased in AD patients, accompanied by declines in brain aminopeptidases A and N, enzymes essential for the synthesis of AngIV. Potent analogs may be useful to counter these changes and facilitate neuronal functioning and reduce apoptosis in memory associated brain structures of AD patients.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:67

Enthalten in:

Journal of Alzheimer's disease : JAD - 67(2019), 2 vom: 13., Seite 469-480

Sprache:

Englisch

Beteiligte Personen:

Wright, John W [VerfasserIn]
Harding, Joseph W [VerfasserIn]

Links:

Volltext

Themen:

Alzheimer’s disease
Ang(1–7)/Mas receptor system
Angiotensin II/AT1 receptor system
Angiotensin IV/AT4 receptor system
Insulin-regulated aminopeptidase (IRAP)
Journal Article
Receptors, Angiotensin
Renin-angiotensin system (RAS)
Research Support, Non-U.S. Gov't
Review

Anmerkungen:

Date Completed 02.03.2020

Date Revised 02.03.2020

published: Print

Citation Status MEDLINE

doi:

10.3233/JAD-181035

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM292922086