Journal of the Renin-Angiotensin-Aldosterone System (Including other Peptidergic systems) Abstract Since the discovery of a renin-angiotensin system (RAS) in the brain, several studies have linked this central RAS to neurological disorders such as ischaemia, Alzheimer's disease and depression. In the last decade, evidence has accumulated that the central RAS might also play a role in Parkinson's disease. Although the exact cause of this progressive neurodegenerative disorder of the basal ganglia remains unidentified, inflammation and oxidative stress have been suggested to be key factors in the pathogenesis and the progression of the disease. Since angiotensin II is a pro-inflammatory compound that can induce the production of reactive oxygen species due to activation of the NADPH-dependent oxidase complex, this peptide might contribute to dopaminergic cell death. In this review, three different strategies to interfere with the pathogenesis or the progression of Parkinson's disease are discussed. They include inhibition of the angiotensin-converting enzyme, blockade of the angiotensin II type 1 receptor and stimulation of the angiotensin II type 2 receptor. Introduction Today, it is widely accepted that the renin-angio-tensin system (RAS) is an important modulator of the salt and water homeostasis, and that angioten-sin II is its major effector peptide. Although at least two receptor subtypes, referred to as the angiotensin II type 1 (AT 1) and angiotensin II type 2 (AT 2) receptor, have been described for angio-tensin II, most of the classical peripheral actions of this peptide, including vasoconstriction, facilitation of sympathetic transmission and renal water and salt retention, are mediated by the AT 1 receptor subtype. 1 In addition to the well-described peripheral RAS, there is now accumulating evidence for the presence of a central RAS. 2,3 In this respect, several studies have linked the central RAS to neurological disorders such as ischaemia,
[1]
Y. Michotte,et al.
Involvement of insulin-regulated aminopeptidase in the effects of the renin–angiotensin fragment angiotensin IV: a review
,
2008,
Heart Failure Reviews.
[2]
M. Phillips,et al.
Brain renin angiotensin in disease
,
2008,
Journal of Molecular Medicine.
[3]
M. Block,et al.
Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism
,
2005,
Progress in Neurobiology.
[4]
J. Brotchie,et al.
Drugs in development for Parkinson's disease.
,
2004,
Current opinion in investigational drugs.
[5]
J. Andersen,et al.
Oxidative stress in neurodegeneration: cause or consequence?
,
2004,
Nature Reviews Neuroscience.
[6]
Anders Björklund,et al.
Prospects for new restorative and neuroprotective treatments in Parkinson's disease
,
1999,
Nature.
[7]
P. Jenner,et al.
Understanding cell death in parkinson's disease
,
1998,
Annals of neurology.
[8]
V. Nahmod,et al.
ANGIOTENSIN AND RENIN IN RAT AND DOG BRAIN
,
1971,
The Journal of experimental medicine.
[9]
E. Nisenbaum,et al.
Neuroreplacement, growth factor, and small molecule neurotrophic approaches for treating Parkinson's disease.
,
2007,
International review of neurobiology.
[10]
T. Unger,et al.
The renin-angiotensin system in the brain: possible therapeutic implications for AT(1)-receptor blockers.
,
2002,
Journal of human hypertension.