Review ARTICLE

Front. Endocrinol., 26 August 2011 | http://dx.doi.org/10.3389/fendo.2011.00017

Angiotensin II, a neuropeptide at the frontier between endocrinology and neuroscience: is there a link between the angiotensin II type 2 receptor and Alzheimer’s disease?

Nicole Gallo-Payet1*, Marie-Odile Guimond1, Lyne Bilodeau1, Charlotta Wallinder2, Mathias Alterman2 and Anders Hallberg2
  • 1 Service of Endocrinology, Department of Medicine, Faculty of Medicine, Centre de recherche clinique Étienne-Le Bel du Centre hospitalier universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada
  • 2 Department of Medicinal Chemistry, Biomedicinska Centrum, Uppsala University, Uppsala, Sweden

Amyloid-β peptide deposition, abnormal hyperphosphorylation of tau, as well as inflammation and vascular damage, are associated with the development of Alzheimer’s disease (AD). Angiotensin II (Ang II) is a peripheral hormone, as well as a neuropeptide, which binds two major receptors, namely the Ang II type 1 receptor (AT1R) and the type 2 receptor (AT2R). Activation of the AT2R counteracts most of the AT1R-mediated actions, promoting vasodilation, decreasing the expression of pro-inflammatory cytokines, both in the brain and in the cardiovascular system. There is evidence that treatment with AT1R blockers (ARBs) attenuates learning and memory deficits. Studies suggest that the therapeutic effects of ARBs may reflect this unopposed activation of the AT2R in addition to the inhibition of the AT1R. Within the context of AD, modulation of AT2R signaling could improve cognitive performance not only through its action on blood flow/brain microcirculation but also through more specific effects on neurons. This review summarizes the current state of knowledge and potential therapeutic relevance of central actions of this enigmatic receptor. In particular, we highlight the possibility that selective AT2R activation by non-peptide and highly selective agonists, acting on neuronal plasticity, could represent new pharmacological tools that may help improve impaired cognitive performance in AD and other neurological cognitive disorders.

Keywords: angiotensin II, angiotensin type 2 receptor, neuron, cognition, brain damage, vasodilation, Alzheimer’s disease

Citation: Gallo-Payet N, Guimond M-O, Bilodeau L, Wallinder C, Alterman M and Hallberg A (2011) Angiotensin II, a neuropeptide at the frontier between endocrinology and neuroscience: is there a link between the angiotensin II type 2 receptor and Alzheimer’s disease? Front. Endocrin. 2:17. doi: 10.3389/fendo.2011.00017

Received: 17 May 2011; Paper pending published: 16 June 2011;
Accepted: 20 July 2011; Published online: 26 August 2011.

Edited by:

Billy K. C. Chow, University of Hong Kong, China

Reviewed by:

Ying-Shing Chan, University of Hong Kong, China
Nicolas Vitale, Centre National de la Recherche Scientifique, France

Copyright: © 2011 Gallo-Payet, Guimond, Bilodeau, Wallinder, Alterman and Hallberg. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Nicole Gallo-Payet, Service d’Endocrinologie, Département de Médecine, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC, Canada J1H 5N4. e-mail: nicole.gallo-payet@usherbrooke.ca