A randomized clinical trial of candesartan for cognitive impairment in Parkinson's disease

Kulisevsky, Jaime; Martínez‐Horta, Saül; Campolongo, Antònia; Pascual‐Sedano, Berta; Marín‐Lahoz, Juan; Bejr‐Kasem, Helena; Labandeira‐Garcia, Jose L.; Lanciego, José L.; Puig-Davi, Arnau; Horta‐Barba, Andrea; Pagonabarraga, Javier; Rodríguez‐Antigüedad, Jon

doi:10.1016/j.parkreldis.2023.105367

Cited by 1 publication

(1 citation statement)

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“…However, the conclusive value of these studies was limited by the low number of patients or other confounding factors such as short periods of exposure to the analyzed drug or the inclusion of different anti-hypertensive drugs or different ARBs and ACE inhibitors in the same group of patients [ 114 ]. More recent studies also suggest the potential clinical effects of ARBs [ 115 , 116 ], including studies using artificial intelligence [ 117 ], which support the neuroprotective effects of AT1 receptor blockers on PD risk. Recent retrospective cohort studies involving a large number of patients are particularly interesting and show that ARBs may be an effective neuroprotective strategy to reduce PD risk and progression [ 118 , 119 ].…”

Section: Introductionmentioning

confidence: 97%

The role of the brain renin-angiotensin system in Parkinson´s disease

Labandeira-Garcia,

Labandeira,

Guerra

et al. 2024

Transl Neurodegener

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The renin-angiotensin system (RAS) was classically considered a circulating hormonal system that regulates blood pressure. However, different tissues and organs, including the brain, have a local paracrine RAS. Mutual regulation between the dopaminergic system and RAS has been observed in several tissues. Dysregulation of these interactions leads to renal and cardiovascular diseases, as well as progression of dopaminergic neuron degeneration in a major brain center of dopamine/angiotensin interaction such as the nigrostriatal system. A decrease in the dopaminergic function induces upregulation of the angiotensin type-1 (AT1) receptor activity, leading to recovery of dopamine levels. However, AT1 receptor overactivity in dopaminergic neurons and microglial cells upregulates the cellular NADPH-oxidase-superoxide axis and Ca2+ release, which mediate several key events in oxidative stress, neuroinflammation, and α-synuclein aggregation, involved in Parkinson's disease (PD) pathogenesis. An intraneuronal antioxidative/anti-inflammatory RAS counteracts the effects of the pro-oxidative AT1 receptor overactivity. Consistent with this, an imbalance in RAS activity towards the pro-oxidative/pro-inflammatory AT1 receptor axis has been observed in the substantia nigra and striatum of several animal models of high vulnerability to dopaminergic degeneration. Interestingly, autoantibodies against angiotensin-converting enzyme 2 and AT1 receptors are increased in PD models and PD patients and contribute to blood–brain barrier (BBB) dysregulation and nigrostriatal pro-inflammatory RAS upregulation. Therapeutic strategies addressed to the modulation of brain RAS, by AT1 receptor blockers (ARBs) and/or activation of the antioxidative axis (AT2, Mas receptors), may be neuroprotective for individuals with a high risk of developing PD or in prodromal stages of PD to reduce progression of the disease.

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