Telmisartan Protects Mitochondrial Function, Gait, and Neuronal Apoptosis by Activating the Akt/GSK3β/PGC1α Pathway in an MPTP-Induced Mouse Model of Parkinson’s Disease.

Bipul, Ray and Sunanda, Tuladhar and Pramod, Gudigenahally Nagaraju and Ashwini, Shivalinga and Mahalakshmi, A. M. and Poornima Priyadarshini, C. G. (2024) Telmisartan Protects Mitochondrial Function, Gait, and Neuronal Apoptosis by Activating the Akt/GSK3β/PGC1α Pathway in an MPTP-Induced Mouse Model of Parkinson’s Disease. Journal of Integrative Neuroscience, 23 (2). p. 29.

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Abstract

Mitochondrial dysfunction is one of the major hallmarks of Parkinson’s disease (PD). Recently, angiotensin II type 1 and type 2 receptors (AT1R, AT2R) were reported to be present on the mitochondrial membrane. Both are crucial players in the brain reninangiotensin system (RAS). Current evidence indicates that blockade of brain AT1R protects dopaminergic neurons in PD. Methods: Thus, the current study was aimed to explore the effects of Telmisartan (Tel), a selective AT1R blocker, on mitochondrial function and a mouse model by exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [250 mg/kg body weight (10 divided i.p. injections, each 25 mg/kg body weight at 3.5 days interval) + Probenecid 250 mg/kg]. Gait function was assessed by beam walk, and mice were euthanized on the 35th day and their brain tissues isolated for Western blot analysis. Results: Pretreatment with Tel significantly protected motor functions during the beam walk in MPTP-treated mice. Tel attenuated the increased levels of AT1R, α-syn, and inflammatory markers such as inducible nitric oxide synthase (iNOS) and ionized calcium-binding adaptor molecule 1 (IBA1) in MPTP-treated mice. In addition, Tel preserved the expression of AT2R, tyrosine hydroxylase (TH), p-Akt/Akt, and p-GSK3β (Ser-9)/GSK3β, as well as protecting mitofusin protein 1 (MFN1) and Peroxisome proliferator-activated receptor-gamma coactivator-α (PGC1α), a critical activator of mitochondrial biogenesis. Conclusion: These results indicate that Tel protects mitochondrial function and gait in a mouse model of PD by modulating the Akt/GSK3β/PGC1α pathway.

Item Type:	Article
Uncontrolled Keywords:	Parkinson’s disease; renin-angiotensin system; mitochondria; telmisartan; MPTP; Adenosine triphosphate (ATP)
Subjects:	500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology
Divisions:	Molecular Nutrition
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	18 Dec 2024 11:02
Last Modified:	18 Dec 2024 11:02
URI:	http://ir.cftri.res.in/id/eprint/18863

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