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PD neuropathology is mainly related to inflammation, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum (ER) stress. The underlying causes for the progression of PD are linked to the uncontrolled activation of different signaling pathways, such as the renin\u2013angiotensin system (RAS), which is highly expressed in the nigrostriatal pathway. RAS has two main pathways: the classical pathway, which includes angiotensin I (AngI), AngII, angiotensin\u2010converting enzyme (ACE), Ang type 1 receptor (AT1R), and Ang type 2 receptor (AT2R), that has a neuro\u2010detrimental effect on PD neuropathology, and the nonclassical pathway, which includes angiotensin\u2010converting enzyme 2 (ACE2)\/Angiotensin 1\u20137 (Ang1\u20137), that has a neuroprotective effect against different neurological disorders, including PD. The nonclassical pathway is activated to overcome the harmful impact of the classical pathway on the brain, thereby converting AngII to angiotensin A (Ang\u2010A) via mononuclear leukocyte\u2010derived aspartate decarboxylase (MILDAD). Ang\u2010A is further converted to the neuroprotective alamandine, which acts on the mass\u2010related G\u2010protein coupled receptor member D (MrgD). In PD, overactivation of the classical pathway is associated with neurodegeneration of the DNs in the SN. However, the nonclassical pathway, mainly Ang1\u20137\/alamandine, is deregulated in PD. The objective of the review: This review aims to explore and discuss the potential role of the nonclassical RAS pathway in the pathogenesis and progression of PD and its implications for future therapeutic strategies.<\/jats:p>","DOI":"10.1002\/brb3.70721","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T07:38:52Z","timestamp":1754984332000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Differential Roles of Angiotensin A and Alamandine in Parkinson's Disease: A Therapeutic Perspective on Nonclassical RAS Pathways"],"prefix":"10.1002","volume":"15","author":[{"given":"Ghadah H.","family":"Alshehri","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy Princess Nourah bint Abdulrahman University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayder 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