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The Renin-Angiotensin System and the Neurodegenerative Diseases: A Brief Review

[ Vol. 24 , Issue. 9 ]

Author(s):

Ana Flavia Almeida-Santos , Lucas M. Kangussu * and Maria Jose Campagnole-Santos*   Pages 841 - 853 ( 13 )

Abstract:


Background: A large body of studies characterized the renal and cardiovascular effects of the peptides of the renin-angiotensin system (RAS). We now recognize that, in addition to angiotensin (Ang) II and Ang III, other peptides, such as, Ang-(1-7), Ang-(1-9), Ang IV and Alamandine can mediate actions of the RAS in different tissues, including the brain. Effects elicited by angiotensins in the brain are complex, site specific and dependent on the interaction with selective receptors, angiotensin type 1 receptor (AT1), AT2, Mas or MrgD, which present widespread distribution in the central nervous system. Although the majority of studies indicate a neuroprotective action for the inhibition of angiotensin converting enzyme or blockade of AT1 receptor, recent studies point to the participation of other angiotensin peptides in the pathophysiology of the neurodegenerative diseases.

Objectives and Methods: In this article, we revised the literature to describe recent findings related to the role of RAS in neurodegenerative diseases such as, Parkinson, Alzheimer, Huntington and Multiple Sclerosis.

Results: The results obtained are promising and may stimulate the development of novel and more effective pharmacological tools to prevent and better control neurodegenerative diseases. In this brief review, we present results from studies showing the participation of the RAS with respect to neurodegenerative diseases, such as, Parkinson, Alzheimer, Huntington and Multiple Sclerosis.

Conclusion: Increased RAS activity leading to increase in Ang II levels, may increase the risk of developing PD, AD, HD or MS. However, the alteration in the balance among angiotensin peptides resulting in increasing Ang-(1-7) or Alamandine may represent effective neuroprotective strategy in population groups at high risk or as coadjutant treatment to reduce the progression of these diseases. Although most studies suggest a neuroprotective action for ACE inhibition or AT1 receptor antagonism, many studies will still be needed to characterize the relative importance (and intracellular mechanisms) of each RAS peptide for the pathophysiology of neurodegenerative diseases. The results to date are promising and may lead to new and more effective pharmacological tools to prevent and better control neurodegenerative diseases.

Keywords:

Angiotensin, Parkinson disease, Alzheimer disease, Huntington disease, Multiple Sclerosis, RAS.

Affiliation:

Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Laboratory of Hypertension, Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627 – ICB, 31270-901; Belo Horizonte, MG, Laboratory of Hypertension, Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627 – ICB, 31270-901; Belo Horizonte, MG

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