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The past few decades have seen an increased emphasis on the involvement of the mitochondrial-associated membrane (MAM) in various neurodegenerative diseases, particularly in Parkinson's disease (PD) and Alzheimer's disease (AD). In PD, alterations in mitochondria, endoplasmic reticulum (ER), and MAM functions affect the secretion and metabolism of proteins, causing an imbalance in calcium homeostasis and oxidative stress. These changes lead to alterations in the translocation of the MAM components, such as IP3R, VDAC, and MFN1 and 2, and consequently disrupt calcium homeostasis and cause misfolded proteins with impaired autophagy, distorted mitochondrial dynamics, and cell death. Various reports indicate the detrimental involvement of the brain renin-angiotensin system (RAS) in oxidative stress, neuroinflammation, and apoptosis in various neurodegenerative diseases. In this review, we attempted to update the reports (using various search engines, such as PubMed, SCOPUS, Elsevier, and Springer Nature) demonstrating the pathogenic interactions between the various proteins present in mitochondria, ER, and MAM with respect to Parkinson's disease. We also made an attempt to speculate the possible involvement of RAS and its components, i.e., AT1 and AT2 receptors, angiotensinogen, in this crosstalk and PD pathology. The review also collates and provides updated information on the role of MAM in calcium signaling, oxidative stress, neuroinflammation, and apoptosis in PD.


Tuladhar Sunanda, Bipul Ray, Arehally M Mahalakshmi, Abid Bhat, Luay Rashan, Wiramon Rungratanawanich, Byoung-Joon Song, Musthafa Mohamed Essa, Meena Kishore Sakharkar, Saravana Babu Chidambaram. Mitochondria-Endoplasmic Reticulum Crosstalk in Parkinson's Disease: The Role of Brain Renin Angiotensin System Components. Biomolecules. 2021 Nov 10;11(11)

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PMID: 34827667

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