Metformin a potential pharmacological strategy in late onset Alzheimer’s disease treatment
| Autor: | Amanda Cano, Jordi Olloquequi, Elena Sánchez-López, Patricia Regina Manzine, Mohammad Javan, Antoni Camins, Saghar Rabiei Poor, Miren Ettcheto |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Fundação de Amparo à Pesquisa do Estado de São Paulo, Iranian National Science Foundation |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
Pharmaceutical Science Review Type 2 diabetes Bioinformatics tau protein hyperphosphorylation Tau protein hiperphosphorylation Insulin resistance Pharmacy and materia medica Diabetes mellitus Drug Discovery Medicine AMP activated protein kinase Cognitive decline AMP activated protein kinase (AMPK) business.industry Liraglutide Insulin Type 2 Diabetes Mellitus Beta amyloid Alzheimer's disease medicine.disease Metformin RS1-441 Molecular Medicine business Alzheimer’s disease medicine.drug |
| Zdroj: | Pharmaceuticals, Vol 14, Iss 890, p 890 (2021) Pharmaceuticals |
| Popis: | 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. This review was funded by the Spanish Ministry of Economy and Competitiveness under the project SAF2017-84283-R, Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED) under project CB06/05/0024 and the European Regional Development Founds. A.C. (Amanda Cano) is supported by the Spanish Ministry of Science, Innovation and Universities under the grant Juan de la Cierva (FJC2018-036012-I). PRM is supported by grants 2015/26084-1 and 2017/13224-5, São Paulo Research Foundation (FAPESP)—Brazil. MJ is supported by the Iranian National Science Foundation grant, INSF-95844516. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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