REVIEW OF ANTI PARKINSONIAN EFFECTS OF ACE INHIBITORS DEMONSTRATED IN VARIOUS ANIMAL AND CLINICAL STUDIES
Parkinsonsâ€™ disease is the second most common neurodegenerative disorder of the world characterized by involuntary muscle movements. It occurs due to degeneration of dopaminergic neurons in substantianigra and deficiency of dopamine in neostriatum. Brain Renin angiotensin system has been identified which is distinct but similar to peripheral renin angiotensin system. It comprises of angiotensin I to IV as mediators; pro-renin receptor, AT1 AT2 and AT4 receptors. Angiotensin converting enzyme (ACE) and AT1 receptor have been identified in substantianigra. Increased activity of ACE and their pro-inflammatory role have been demonstrated in animal models of parkinsonsâ€™ disease. Anti-inflammatory action of certain ACE inhibitors and Angiotensin Receptor Blockers (ARBâ€™s) in Parkinson induced neurons have also been demonstrated in animal models. The preceding findings have also been identified in some clinical studies.Â
Olanow CW, Schapira AHV. Parkinson's Disease and Related Disorders. In: Longo, Fauci, Kasper, Hauser, Jameson, Loscalzo, editors. Harrisonâ€™s principles of internal medicine. 18th ed. USA:McGraw Hill;2012.p3317-3333.
Shan Z, Cuadra AE, Sumners C, Raizada MK. Characterization of a functional (pro)renin receptor in rat brain neurons. Exp Physiol 2008:93;701â€“8.
Lippoldt A, Paul M, Fuxe K, Ganten D. The brain reninâ€“angiotensin system â€“ molecular mechanisms of cell-to-cell interactions. Clin Exp Hypertension 1995;17: 251â€“66.
Ferrario CM, Barnes KL, Block CH, Brosnihan KB, Diz DI, Khosla MC et al. Pathways of angiotensin formation and function in the brain. Hypertension 1990;15: I13â€“I19.
Alexander SP, Mathie A, Peters JA. Guide to Receptors and Channels, 3rd ed. Br J Pharmacol. 2008; 153 Suppl 2: S1â€“S209.
Reagan LP, Flanagan-Cato LM, Yee DK, Ma LY, Sakai RR, Fluharty SJ. Immunohistochemical mapping of angiotensin type 2(AT2) receptors in rat brain. Brain Res 1994: 662; 45â€“59.
Albiston AL, McDowall SG, Matsacos D, Sim P, Clune E, Mustafa T et al. Evidence that the angiotensin IV (AT4) receptor is the enzyme insulin-regulated aminopeptidase. J BiolChem 2001; 276:48623â€“6.
Rodriguez-Pallares J, Rey P, Parga JA, Munoz A, Guerra MJ, Labandeira-Garcia JL. Brain angiotensin enhances dopaminergic cell death via microglial activation and NADPH-derived ROS. NeurobiolDis 2008;31: 58â€“73.
Rey P, Lopez-Real A, Sanchez-Iglesias S, Munoz A, Soto-Otero R, Labandeira-Garcia JL. Angiotensin type-1-receptor antagonists reduce 6-hydroxydopamine toxicity for dopaminergicneurons. Neurobiol Aging. 2007: 28; 555â€“567.
Grammatopoulos TN, Outeiro TF, Hyman BT, Standaert DG. Angiotensin II protects against alpha-synuclein toxicity and reduces protein aggregation in vitro. BiochemBiophys Res Commun 2007;363:846â€“51.
Allen AM, MacGregor DP, Chai SY, Donnan GA, Kaczmarczyk S, Richardson K. et al. Angiotensin II receptor binding associated with nigrostriatal dopaminergic neurons in human basal ganglia. Annals of neurology 1992; 32 (3): 339-44.
Okamura A, Rakugi H, Ohishi M, Yanagitani Y, Takiuchi S, Moriguchi K, et al. Upregulation of renin-angiotensin system during differentiation of monocytes to macrophages. Journal of hypertension 1999; 17(4): 537-45.
Rodriguez-Pallares, Quiroz CR, Parga JA, Guerra MJ, Labandeira-Garcia JL. Angiotensin II increases differentiation of dopaminergic neurons from mesencephalic precursors via angiotensin type 2 receptors. European journal of neuroscience 2004; 20(6): 1489-98.
Rodriguez-Pallares J, Rey P, Parga JA, Munoz A, Guerra MJ, Labandeira-Garcia JL. Brain angiotensin enhances dopaminergic cell death via microglial activation and NADPH derived ROS. Neurobiology of disease 2008; 31(1): 58-73.
Lopez-Real A, Rey P, Soto-Otero R, Mendez-Alvarez E, Labandeira-Garcia JL. Angiotensin-converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6-hydroxydopamine rat model of parkinsonism. J Neurosci Res 2005;81:865â€“73.
Rey P, Lopez-Real A, Sanchez-Iglesias S, Munoz A, Soto-Otero R, Labandeira-Garcia JL. Angiotensin type-1-receptor antagonists reduce 6-hydroxydopamine toxicity for dopaminergic neurons. Neurobiol Aging 2007; 28: 555â€“67.
Reardon KA, Mendelsohn FA, Chai SY, Horne MK. The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifiesthe clinical features of Parkinsonâ€™s disease. Aust N Z J Med. 2000: 30; 48â€“53.
Jenkins TA, Mendelsohn FAO, Chai SY. Angiotensin-converting enzyme modulates dopamine turnover in the striatum. Journal of Neurochemistry 1997; 68(3): 1304â€“11.
Munoz A, Rey P, Guerra MJ, Mendez-Alvarez E, Soto-Otero R, Labandeira-Garcia JL. Reduction of dopaminergic degeneration and oxidative stress by inhibition of angiotensin converting enzyme in a MPTP model of parkinsonism. Neuropharmacology 2006; 51( 1); 112â€“20.
Rodriquez-Perez I, Dominquez-Meijide A, Lanciego JL, Guerra MJ, Labandeira-Garcia JL. Dopaminergic degeneration is enhanced by chronic brain hypoperfusion and inhibited by angiotensin receptor blockage. Age (Dordr). Epub 2012 Sep 18.
Doris Albrecht. Physiological and pathophysiological functions of different angiotensins in the brain. British Journal of Pharmacology 2010; 159:1392-401.
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