The role of the central renin-angiotensin system in Parkinson’s disease

Mertens, Birgit; Vanderheyden, Patrick; Michotte, Yvette; Sarre, Sophie

doi:10.1177/1470320309347789

Cited by 87 publications

(79 citation statements)

References 94 publications

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“…Angiotensin II (Ang II) is the major effector of RAS, and most of its classical peripheral functions were medicated by Ang II type 1 receptor (AT1R) [2]. Recently, numerous studies have demonstrated that independent RAS existed in many other tissues and organs including the brain [3–5].…”

Section: Introductionmentioning

confidence: 99%

Azilsartan ameliorates apoptosis of dopaminergic neurons and rescues characteristic parkinsonian behaviors in a rat model of Parkinson’s disease

Gao

Jiang

et al. 2017

Oncotarget

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Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinsons disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased. Furthermore, we provided in vivo evidence that Ang II directly elicited apoptosis of dopaminergic neurons via activation of AT1R in the SN of rats. More importantly, we showed for the first time that oral administration of azilsartan, a newly developed AT1R blocker approved by the U.S. Food and Drug Administration for hypertension treatment, rescued the apoptosis of dopaminergic neurons and relieved the characteristic parkinsonian symptoms in PD rats. These results support the application of AT1R blockers in PD therapy, and strengthen the notion that many therapeutic agents may possess pleiotropic action in addition to their main applications.

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Section: Introductionmentioning

confidence: 99%

Azilsartan ameliorates apoptosis of dopaminergic neurons and rescues characteristic parkinsonian behaviors in a rat model of Parkinson’s disease

Gao

Jiang

et al. 2017

Oncotarget

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“…This system acts as a regulator of fluid homeostasis, blood pressure, sexual behavior, and stress responses (184). The CNS RAS might be involved not only in the development of cardiovascular disease (30) but also in neuroinflammation, in particular in PD (99,121).…”

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confidence: 99%

New Insights onNOXEnzymes in the Central Nervous System

Nayernia

Jaquet

Krause

2014

Antioxidants & Redox Signaling

248

231

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Significance: There is increasing evidence that the generation of reactive oxygen species (ROS) in the central nervous system (CNS) involves the NOX family of nicotinamide adenine dinucleotide phosphate oxidases. Controlled ROS generation appears necessary for optimal functioning of the CNS through fine-tuning of redoxsensitive signaling pathways, while overshooting ROS generation will lead to oxidative stress and CNS disease. Recent Advances: NOX enzymes are not only restricted to microglia (i.e. brain phagocytes) but also expressed in neurons, astrocytes, and the neurovascular system. NOX enzymes are involved in CNS development, neural stem cell biology, and the function of mature neurons. While NOX2 appears to be a major source of pathological oxidative stress in the CNS, other NOX isoforms might also be of importance, for example, NOX4 in stroke. Globally speaking, there is now convincing evidence for a role of NOX enzymes in various neurodegenerative diseases, cerebrovascular diseases, and psychosis-related disorders. Critical Issues: The relative importance of specific ROS sources (e.g., NOX enzymes vs. mitochondria; NOX2 vs. NOX4) in different pathological processes needs further investigation. The absence of specific inhibitors limits the possibility to investigate specific therapeutic strategies. The uncritical use of non-specific inhibitors (e.g., apocynin, diphenylene iodonium) and poorly validated antibodies may lead to misleading conclusions. Future Directions: Physiological and pathophysiological studies with cell-type-specific knock-out mice will be necessary to delineate the precise functions of NOX enzymes and their implications in pathomechanisms. The development of CNS-permeant, specific NOX inhibitors will be necessary to advance toward therapeutic applications. Antioxid. Redox Signal. 20, 2815Signal. 20, -2837

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“…53 Combined receptor antagonism with losartan and PD123319 has shown beneficial effects on in vitro genetic model of PD, having raised content of α-synuclein and over-expression of the human neuroglioma H4 cell line. 54 In PD, Ang II produced therapeutic action via AT1 R, which is considered as one of the most important known inducers of neuroinflammation and oxidative stress by activation of the reduced NADPH-oxidase complex. AT1 and AT2 receptors have been located in dopamine (DA) neurons, microglia, and astrocytes.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Cerebroprotective effects of RAS inhibitors: Beyond their cardio-renal actions

Kalra

Prakash

Kumar

et al. 2015

J Renin Angiotensin Aldosterone Syst

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Work on the brain renin–angiotensin system has been explored by various researchers and has led to elucidation of its basic physiologies and behavior, including its role in reabsorption and uptake of body fluid, blood pressure maintenance with angiotensin II being its prominent effector. Currently, this system has been implicated for its newly established effects, which are far beyond its cardio-renal effects accounting for maintenance of cerebral blood flow and cerebroprotection, seizure, in the etiology of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and bipolar disorder. In this review, we have discussed the distribution of angiotensin receptor subtypes in the central nervous system (CNS) together with enzymatic pathways leading to active angiotensin ligands and its interaction with angiotensin receptor 2 (AT2) and Mas receptors. Secondly, the use of angiotensin analogues (angiotensin converting enzyme inhibitors and AT1 and/or AT2 receptor blockers) in the treatment and management of the CNS disorders mentioned above has been discussed.

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The role of the central renin-angiotensin system in Parkinson’s disease

Cited by 87 publications

References 94 publications

Azilsartan ameliorates apoptosis of dopaminergic neurons and rescues characteristic parkinsonian behaviors in a rat model of Parkinson’s disease

Azilsartan ameliorates apoptosis of dopaminergic neurons and rescues characteristic parkinsonian behaviors in a rat model of Parkinson’s disease

New Insights onNOXEnzymes in the Central Nervous System

Cerebroprotective effects of RAS inhibitors: Beyond their cardio-renal actions

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