The classical and non-classical axes of renin-angiotensin system in Parkinson disease: The bright and dark side of the moon

• Published in: Ageing research reviews 2024-02, Vol.94, p.102200, Article 102200
• Main Authors: Al-kuraishy, Hayder M., Al-Hamash, Sadiq M., Jabir, Majid S., Al-Gareeb, Ali I., Albuhadily, Ali K., Albukhaty, Salim, Sulaiman, Ghassan M.
• Format: Article
• Language: English
• Subjects: Angiotensin II - metabolism; Classical renin-angiotensin system axis; Humans; Hypertension; Neurodegenerative Diseases; Non-classical renin-angiotensin system axis; Parkinson Disease; Peptidyl-Dipeptidase A - metabolism; Renin-angiotensin system; Renin-Angiotensin System - physiology
• ISSN: 1568-1637; 1872-9649; 1872-9649
• DOI: 10.1016/j.arr.2024.102200

Parkinson disease (PD) is a common brain neurodegenerative disease due to progressive degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). Of note, the cardio-metabolic disorders such as hypertension are adversely affect PD neuropathology through exaggeration of renin-angiotensin system (RAS). The RAS affects the stability of dopaminergic neurons in the SNpc, and exaggeration of angiotensin II (AngII) is implicated in the development and progression of PD. RAS has two axes classical including angiotensin converting enzyme (ACE)/AngII/AT1R, and the non-classical axis which include ACE2/Ang1–7/Mas receptor, AngIII, AngIV, AT2R, and AT4R. It has been shown that brain RAS is differs from that of systemic RAS that produce specific neuronal effects. As well, there is an association between brain RAS and PD. Therefore, this review aims to revise from published articles the role of brain RAS in the pathogenesis of PD focusing on the non-classical pathway, and how targeting of this axis can modulate PD neuropathology. •PD neuropathology may be associated with the exaggeration of brain RAS.•The classical pathway of brain RAS has a harmful effect on the dopaminergic neurons in the SNpc.•The non-classical pathway of brain RAS counteracts the detrimental effect of the classical pathway of brain RAS.•ARBs and ACEIs have neuroprotective effects against PD by reducing and increasing the classical and non-classical pathways.