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

PEREZ-LLORET S, OTERO-LOSADA M, TOBLLI JE, CAPANI F

EXPERT OPINION ON INVESTIGATIONAL DRUGS

INFORMA HEALTHCARE

Lugar: London; Año: 2017

1354-3784

Introduction: Currently, available therapies for Parkinson?s disease (PD) aresymptomatic. Therefore, the search for neuroprotective drugs remains a toppriority.Areas covered: In this review, the potential symptomatic or disease-modifyingeffect of drugs targeting the Renin-Angiotensin System (RAS) in PD will beexplored.Expert opinion: The importance of nigrostriatal local RAS has only begun to beunraveled in the last decades. On one hand, there is a complex feedback cyclebetween RAS and dopamine (DA). On the other hand, RAS affectsdopaminergic neurons vulnerability. Neuroprotective effects in animal PDmodels 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 areduction in the overproduction of reactive oxygen species (ROS). In a proof-ofconcept,randomized, double-blind, crossover study in PD patients, perindoprilenhanced the effect of levodopa without inducing dyskinesias. There has notbeen any clinical trial exploring the neuroprotective effect of RAS drugs, but onecohort study in hypertensive patients suggested a protective effect of ACEinhibitors on PD risk. RAS is a promising target for symptomatic andDownloaded by [Australian Catholic University] at 05:09 25 August 2017 Accepted Manuscript3neuroprotective therapies in PD. Further studies in PD animal models andpatients are warranted