Repurposing Metformin to Treat Age-related Neurodegenerative Disorders and Ischemic Stroke

Overview

Journal Life Sci

Publisher Elsevier

Specialties Biochemistry
Biology
Physiology

Date 2021 Mar 15

PMID 33716063

Citations 30

Authors

Sejal Sharma

Saeideh Nozohouri

Bhuvaneshwar Vaidya

Thomas Abbruscato

Affiliations

Soon will be listed here.

Abstract

Aging is a risk factor for major central nervous system (CNS) disorders. More specifically, aging can be inked to neurodegenerative diseases (NDs) because of its deteriorating impact on neurovascular unit (NVU). Metformin, a first line FDA-approved anti-diabetic drug, has gained increasing interest among researchers for its role in improving aging-related neurodegenerative disorders. Additionally, numerous studies have illustrated metformin's role in ischemic stroke, a cerebrovascular disorder in which the NVU becomes dysfunctional which can lead to permanent life-threatening disabilities. Considering metformin's beneficial preclinical actions on various disorders, and the drug's role in alleviating severity of these conditions through involvement in commonly characterized cellular pathways, we discuss the potential of metformin as a suitable drug candidate for repurposing in CNS disorders.

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References

DeGracia D . Towards a dynamical network view of brain ischemia and reperfusion. Part I: background and preliminaries. J Exp Stroke Transl Med. 2011; 3(1):59-71. PMC: 3082153. DOI: 10.6030/1939-067x-3.1.59. View

Ashabi G, Khodagholi F, Khalaj L, Goudarzvand M, Nasiri M . Activation of AMP-activated protein kinase by metformin protects against global cerebral ischemia in male rats: interference of AMPK/PGC-1α pathway. Metab Brain Dis. 2014; 29(1):47-58. DOI: 10.1007/s11011-013-9475-2. View

Markowicz-Piasecka M, Huttunen K, Mateusiak L, Mikiciuk-Olasik E, Sikora J . Is Metformin a Perfect Drug? Updates in Pharmacokinetics and Pharmacodynamics. Curr Pharm Des. 2016; 23(17):2532-2550. DOI: 10.2174/1381612822666161201152941. View

Lakhan S, Kirchgessner A, Hofer M . Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med. 2009; 7:97. PMC: 2780998. DOI: 10.1186/1479-5876-7-97. View

Gitler A, Dhillon P, Shorter J . Neurodegenerative disease: models, mechanisms, and a new hope. Dis Model Mech. 2017; 10(5):499-502. PMC: 5451177. DOI: 10.1242/dmm.030205. View

Kaisar M, Villalba H, Prasad S, Liles T, Sifat A, Sajja R . Offsetting the impact of smoking and e-cigarette vaping on the cerebrovascular system and stroke injury: Is Metformin a viable countermeasure?. Redox Biol. 2017; 13:353-362. PMC: 5480985. DOI: 10.1016/j.redox.2017.06.006. View

Karimipour M, Shojaei Zarghani S, Mohajer Milani M, Soraya H . Pre-Treatment with Metformin in Comparison with Post-Treatment Reduces Cerebral Ischemia Reperfusion Induced Injuries in Rats. Bull Emerg Trauma. 2018; 6(2):115-121. PMC: 5928267. DOI: 10.29252/beat-060205. View

Brown W, Thore C . Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol. 2010; 37(1):56-74. PMC: 3020267. DOI: 10.1111/j.1365-2990.2010.01139.x. View

Wang P, Fang H, Chen J, Lin S, Liu Y, Xiong X . Polyinosinic-polycytidylic acid has therapeutic effects against cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via TLR3. J Immunol. 2014; 192(10):4783-94. PMC: 4009499. DOI: 10.4049/jimmunol.1303108. View

10.

Toornvliet R, van Berckel B, Luurtsema G, Lubberink M, Geldof A, Bosch T . Effect of age on functional P-glycoprotein in the blood-brain barrier measured by use of (R)-[(11)C]verapamil and positron emission tomography. Clin Pharmacol Ther. 2006; 79(6):540-8. DOI: 10.1016/j.clpt.2006.02.004. View

11.

Adams J . Smoking Cessation-Progress, Barriers, and New Opportunities: The Surgeon General's Report on Smoking Cessation. JAMA. 2020; 323(24):2470-2471. DOI: 10.1001/jama.2020.6647. View

12.

Erickson M, Banks W . Age-Associated Changes in the Immune System and Blood⁻Brain Barrier Functions. Int J Mol Sci. 2019; 20(7). PMC: 6479894. DOI: 10.3390/ijms20071632. View

13.

Gupta A, Bisht B, Dey C . Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer's-like changes. Neuropharmacology. 2011; 60(6):910-20. DOI: 10.1016/j.neuropharm.2011.01.033. View

14.

Osellame L, Duchen M . Defective quality control mechanisms and accumulation of damaged mitochondria link Gaucher and Parkinson diseases. Autophagy. 2013; 9(10):1633-5. DOI: 10.4161/auto.25878. View

15.

Abbott N, Patabendige A, Dolman D, Yusof S, Begley D . Structure and function of the blood-brain barrier. Neurobiol Dis. 2009; 37(1):13-25. DOI: 10.1016/j.nbd.2009.07.030. View

16.

Wrobel M, Marek B, Kajdaniuk D, Rokicka D, Szymborska-Kajanek A, Strojek K . Metformin - a new old drug. Endokrynol Pol. 2017; 68(4):482-496. DOI: 10.5603/EP.2017.0050. View

17.

Pelegri C, Canudas A, Del Valle J, Casadesus G, Smith M, Camins A . Increased permeability of blood-brain barrier on the hippocampus of a murine model of senescence. Mech Ageing Dev. 2007; 128(9):522-8. DOI: 10.1016/j.mad.2007.07.002. View

18.

Goodarzi M, Bryer-Ash M . Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents. Diabetes Obes Metab. 2005; 7(6):654-65. DOI: 10.1111/j.1463-1326.2004.00448.x. View

19.

Chiang M, Cheng Y, Chen S, Yen C, Huang R . Metformin activation of AMPK-dependent pathways is neuroprotective in human neural stem cells against Amyloid-beta-induced mitochondrial dysfunction. Exp Cell Res. 2016; 347(2):322-31. DOI: 10.1016/j.yexcr.2016.08.013. View

20.

Sarkaki A, Farbood Y, Badavi M, Khalaj L, Khodagholi F, Ashabi G . Metformin improves anxiety-like behaviors through AMPK-dependent regulation of autophagy following transient forebrain ischemia. Metab Brain Dis. 2015; 30(5):1139-50. DOI: 10.1007/s11011-015-9677-x. View