IMR Press / JIN / Volume 23 / Issue 2 / DOI: 10.31083/j.jin2302029
Open Access Original Research
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
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1 Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), 570015 Mysuru, India
2 Centre for Experimental Pharmacology and Toxicology, Central Animal Facility, JSS Academy of Higher Education & Research, 570015 Mysuru, India
3 Section of Molecular Pharmacology and Toxicology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA
4 Department of Molecular Nutrition, Council of Scientific and Industrial Research (CSIR)—Central Food Technological Research Institute, 570020 Mysuru, India
5 Council of Scientific and Industrial Research (CSIR), Academy of Scientific and Innovative Research (AcSIR), 201002 Ghaziabad, India
6 Brain, Behavior and Cognitive Neurosciences Research (BBCR), JSS Academy of Higher Education & Research, 570015 Mysuru, India
*Correspondence:; (Saravana Babu Chidambaram)
J. Integr. Neurosci. 2024, 23(2), 29;
Submitted: 31 August 2023 | Revised: 16 October 2023 | Accepted: 18 October 2023 | Published: 4 February 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: 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 renin-angiotensin 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.

Parkinson's disease
renin-angiotensin system
Adenosine triphosphate (ATP)
No-45/3/2019-PHA/BMS/OL/Indian Council of Medical Research (ICMR)
Fig. 1.
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