The angiotensin-converting enzyme (<i>ACE</i>) I/D polymorphism in Parkinson’s disease

Su, Gang; Dou, Huan; Zhao, Limei; Wang, Hongjie; Liu, Guiyang; Huang, Bo; Peng, Bo

doi:10.1177/1470320313494432

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…The results were independent of the presence of hypertension, hyperlipemia, stroke, or smoking. However, other studies reported no such association in non-Chinese PD patients and controls [69,75].…”

Section: Alterations Of the Ras Pathway In Pd Patientsmentioning

confidence: 88%

Renin-angiotensin system as a potential target for new therapeutic approaches in Parkinson’s disease

Pérez-Lloret

Otero‐Losada

Toblli

et al. 2017

Expert Opinion on Investigational Drugs

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Currently, available therapies for Parkinson's disease (PD) are symptomatic. Therefore, the search for neuroprotective drugs remains a top priority. Areas covered: In this review, the potential symptomatic or disease-modifying effect of drugs targeting the Renin-Angiotensin System (RAS) in PD will be explored. Expert opinion: The importance of nigrostriatal local RAS has only begun to be unraveled in the last decades. On one hand, there is a complex feedback cycle between RAS and dopamine (DA). On the other hand, RAS affects dopaminergic neurons vulnerability. Neuroprotective effects in animal PD models have been shown for the angiotensin-converting enzyme (ACE) inhibitors captopril and perindopril, and the AT1 receptor antagonists losartan, candesartan and telmisartan. These effects appear to be mediated by a reduction in the overproduction of reactive oxygen species. In a proof-of-concept, randomized, double-blind, crossover study in PD patients, perindopril enhanced the effect of levodopa without inducing dyskinesias. There has not been any clinical trial exploring the neuroprotective effect of RAS drugs, but one cohort study in hypertensive patients suggested a protective effect of ACE inhibitors on PD risk. RAS is a promising target for symptomatic and neuroprotective therapies in PD. Further studies in PD animal models and patients are warranted.

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Section: Alterations Of the Ras Pathway In Pd Patientsmentioning

confidence: 88%

Renin-angiotensin system as a potential target for new therapeutic approaches in Parkinson’s disease

Pérez-Lloret

Otero‐Losada

Toblli

et al. 2017

Expert Opinion on Investigational Drugs

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“…To date, meta-analyses on human subjects have not provided explicit evidence for the association between ACE gene I/D polymorphism and PD risk [259].…”

Section: Ras In Parkinson's Disease and Tardive Dyskinesiamentioning

confidence: 99%

Multiple Aspects of Inappropriate Action of Renin–Angiotensin, Vasopressin, and Oxytocin Systems in Neuropsychiatric and Neurodegenerative Diseases

Szczepañska‐Sadowska

Wsol

Cudnoch‐Jędrzejewska

et al. 2022

JCM

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The cardiovascular system and the central nervous system (CNS) closely cooperate in the regulation of primary vital functions. The autonomic nervous system and several compounds known as cardiovascular factors, especially those targeting the renin–angiotensin system (RAS), the vasopressin system (VPS), and the oxytocin system (OTS), are also efficient modulators of several other processes in the CNS. The components of the RAS, VPS, and OTS, regulating pain, emotions, learning, memory, and other cognitive processes, are present in the neurons, glial cells, and blood vessels of the CNS. Increasing evidence shows that the combined function of the RAS, VPS, and OTS is altered in neuropsychiatric/neurodegenerative diseases, and in particular in patients with depression, Alzheimer’s disease, Parkinson’s disease, autism, and schizophrenia. The altered function of the RAS may also contribute to CNS disorders in COVID-19. In this review, we present evidence that there are multiple causes for altered combined function of the RAS, VPS, and OTS in psychiatric and neurodegenerative disorders, such as genetic predispositions and the engagement of the RAS, VAS, and OTS in the processes underlying emotions, memory, and cognition. The neuroactive pharmaceuticals interfering with the synthesis or the action of angiotensins, vasopressin, and oxytocin can improve or worsen the effectiveness of treatment for neuropsychiatric/neurodegenerative diseases. Better knowledge of the multiple actions of the RAS, VPS, and OTS may facilitate programming the most efficient treatment for patients suffering from the comorbidity of neuropsychiatric/neurodegenerative and cardiovascular diseases.

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“…Circulating Ang II is generated from Ang I by ACE carboxypeptidase activity in the pulmonary endothelial cells (Herichova and Szantoova, 2013;Su et al, 2015), and its effects are mediated mainly via AT1R receptors. The RAS axis is of scientific, medical, and pharmacological interest owing to its effects on blood pressure and heart hypertrophy (Herichova and Szantoova, 2013) (Figure 1).…”

Section: General Organization Of the Renin-angiotensin Systemmentioning

confidence: 99%

The Renin–Angiotensin System Modulates Dopaminergic Neurotransmission: A New Player on the Scene

Kobiec

Otero‐Losada

Chevalier

et al. 2021

Front. Synaptic Neurosci.

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Parkinson’s disease (PD) is an extrapyramidal disorder characterized by neuronal degeneration in several regions of the peripheral and central nervous systems. It is the second most frequent neurodegenerative disease after Alzheimer’s. It has become a major health problem, affecting 1% of the world population over 60 years old and 3% of people beyond 80 years. The main histological findings are intracellular Lewy bodies composed of misfolded α-synuclein protein aggregates and loss of dopaminergic neurons in the central nervous system. Neuroinflammation, apoptosis, mitochondrial dysfunction, altered calcium homeostasis, abnormal protein degradation, and synaptic pathobiology have been put forward as mechanisms leading to cell death, α-synuclein deposition, or both. A progressive loss of dopaminergic neurons in the substantia nigra late in the neurodegeneration leads to developing motor symptoms like bradykinesia, tremor, and rigidity. The renin–angiotensin system (RAS), which is involved in regulating blood pressure and body fluid balance, also plays other important functions in the brain. The RAS is involved in the autocrine and paracrine regulation of the nigrostriatal dopaminergic synapses. Dopamine depletion, as in PD, increases angiotensin II expression, which stimulates or inhibits dopamine synthesis and is released via AT1 or AT2 receptors. Furthermore, angiotensin II AT1 receptors inhibit D1 receptor activation allosterically. Therefore, the RAS may have an important modulating role in the flow of information from the brain cortex to the basal ganglia. High angiotensin II levels might even aggravate neurodegeneration, activating the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, which leads to increased reactive oxygen species production.

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The angiotensin-converting enzyme (ACE) I/D polymorphism in Parkinson’s disease

Cited by 6 publications

References 14 publications

Renin-angiotensin system as a potential target for new therapeutic approaches in Parkinson’s disease

Renin-angiotensin system as a potential target for new therapeutic approaches in Parkinson’s disease

Multiple Aspects of Inappropriate Action of Renin–Angiotensin, Vasopressin, and Oxytocin Systems in Neuropsychiatric and Neurodegenerative Diseases

The Renin–Angiotensin System Modulates Dopaminergic Neurotransmission: A New Player on the Scene

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