Metformin - a Future Therapy for Neurodegenerative Diseases : Theme: Drug Discovery, Development and Delivery in Alzheimer's Disease Guest Editor: Davide Brambilla.

Abstract

Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer's disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties. Recently, scientists have put their efforts in establishing metformin's role in the treatment of neurodegenerative diseases, such as AD, amnestic mild cognitive impairment and Parkinson's disease. Results of several clinical studies confirm that long term use of metformin in diabetic patients contributes to better cognitive function, compared to participants using other anti-diabetic drugs. The exact mechanism of metformin's advantageous activity in AD is not fully understood, but scientists claim that activation of AMPK-dependent pathways in human neural stem cells might be responsible for the neuroprotective activity of metformin. Metformin was also found to markedly decease Beta-secretase 1 (BACE1) protein expression and activity in cell culture models and in vivo, thereby reducing BACE1 cleavage products and the production of Aβ (β-amyloid). Furthermore, there is also some evidence that metformin decreases the activity of acetylcholinesterase (AChE), which is responsible for the degradation of acetylcholine (Ach), a neurotransmitter involved in the process of learning and memory. In regard to the beneficial effects of metformin, its anti-inflammatory and anti-oxidative properties cannot be omitted. Numerous in vitro and in vivo studies have confirmed that metformin ameliorates oxidative damage.

• Authors: Magdalena Markowicz-Piasecka, Joanna Sikora, Aleksandra Szydłowska, Agata Skupień, Elżbieta Mikiciuk-Olasik, Kristiina M Huttunen
• Journal: Pharmaceutical research (Pharm Res) Vol. 34 Issue 12 Pg. 2614-2627 (Dec 2017) ISSN: 1573-904X [Electronic] United States
• PMID: 28589443 (Publication Type: Journal Article, Review)

Chemical References

• Amyloid beta-Peptides
• Antioxidants
• Cholinesterase Inhibitors
• Hypoglycemic Agents
• Metformin
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Alzheimer Disease (drug therapy, metabolism)
• Amyloid beta-Peptides (metabolism)
• Animals
• Antioxidants (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Cholinesterase Inhibitors (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism)
• Drug Discovery
• Humans
• Hypoglycemic Agents (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Metformin (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Oxidative Stress (drug effects)