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

ABSTRACT

Introduction: 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.

KEYWORDS:

• Parkinson’s disease
• neuroprotection
• treatment
• renin
• angiotensin

Article highlights

• There is a complex feedback cycle between the Renin-Angiotensin System (RAS) and striatal dopamine (DA) tone.

• 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.

• In a proof-of-concept, randomized, double-blind, crossover study in PD patients, perindopril enhanced the effect of levodopa without inducing dyskinesias.

• A large 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.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

National Scientific and Technical Research Council (PIP 11420100100159, CONICET, Argentina) and the University of Buenos Aires (UBACYT).