Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer's Disease Treatment

Author(s)

Poor, Saghar Rabiei ^{[1, 2, 3]} ; Ettcheto, Miren ^{[3, 4]} ; Cano, Amanda ^{[4, 5, 6, 7]} ; Sanchez-Lopez, Elena ^{[4, 6, 7]} ; Manzine, Patricia Regina ^{[8, 3]} ; Olloquequi, Jordi ^[9] ; Camins, Antoni ^{[3, 4, 5, 9]} ; Javan, Mohammad ^{[1, 2, 10]}

Affiliation

^[1] Tarbiat Modares Univ, Dept Physiol, Fac Med Sci, Tehran 1411713116 - Iran

^[2] Tarbiat Modares Univ, Inst Brain & Cognit, Tehran 1411713116 - Iran

^[3] Univ Barcelona, Dept Pharmacol Toxicol & Therapeut Chem, Fac Pharm & Food Sci, Inst Neurociencies, Barcelona 08028 - Spain

^[4] Biomed Res Networking Ctr Neurodegenerat Dis CIBE, Madrid 08028 - Spain

^[5] Univ Int Catalunya UIC, Ace Alzheimer Ctr Barcelona, Barcelona 08028 - Spain

^[6] Inst Nanosci & Nanotechnol IN2UB, Barcelona 08028 - Spain

^[7] Univ Barcelona, Fac Pharm & Food Sci, Dept Pharm Pharmaceut Technol & Phys Chem, Barcelona 08028 - Spain

^[8] Fed Univ Sao Carlos UFSCar, Dept Gerontol, BR-13565905 Sao Carlos - Brazil

^[9] Univ Autonoma Chile, Lab Cellular & Mol Pathol, Inst Biomed Sci, Fac Hlth Sci, Talca 3467987 - Chile

^[10] ACECR, Dept Brain & Cognit Sci, Cell Sci Res Ctr, Royan Inst Stem Cell Biol & Technol, Tehran 1411713116 - Iran

• Document type: Review article
• Source: PHARMACEUTICALS; v. 14, n. 9 SEP 2021.
• Web of Science Citations: 0

Abstract

Alzheimer's disease (AD) is one of the most devastating brain disorders. Currently, there are no effective treatments to stop the disease progression and it is becoming a major public health concern. Several risk factors are involved in the progression of AD, modifying neuronal circuits and brain cognition, and eventually leading to neuronal death. Among them, obesity and type 2 diabetes mellitus (T2DM) have attracted increasing attention, since brain insulin resistance can contribute to neurodegeneration. Consequently, AD has been referred to ``type 3 diabetes{''} and antidiabetic medications such as intranasal insulin, glitazones, metformin or liraglutide are being tested as possible alternatives. Metformin, a first line antihyperglycemic medication, is a 5 `-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activator hypothesized to act as a geroprotective agent. However, studies on its association with age-related cognitive decline have shown controversial results with positive and negative findings. In spite of this, metformin shows positive benefits such as anti-inflammatory effects, accelerated neurogenesis, strengthened memory, and prolonged life expectancy. Moreover, it has been recently demonstrated that metformin enhances synaptophysin, sirtuin-1, AMPK, and brain-derived neuronal factor (BDNF) immunoreactivity, which are essential markers of plasticity. The present review discusses the numerous studies which have explored (1) the neuropathological hallmarks of AD, (2) association of type 2 diabetes with AD, and (3) the potential therapeutic effects of metformin on AD and preclinical models. (AU)

• FAPESP's process: 17/13224-5 - Study of the JNK1 pathway as a selective target for the treatment of cognitive metabolic disorder: ADAM10 protein analysis
• Grantee: Patricia Regina Manzine Moralles
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 15/26084-1 - Evaluation of platelet ADAM10 in non-Alzheimer's dementias
• Grantee: Patricia Regina Manzine Moralles
• Support Opportunities: Scholarships in Brazil - Post-Doctoral