AMPK activators for the prevention and treatment of neurodegenerative diseases

ABSTRACT

Introduction

As the global population ages at an unprecedented rate, the burden of neurodegenerative diseases is expected to grow. Given the profound impact illness like dementia exert on individuals and society writ large, researchers, physicians, and scientific organizations have called for increased investigation into their treatment and prevention. Both metformin and aspirin have been associated with improved cognitive outcomes. These agents are related in their ability to stimulate AMP kinase (AMPK). Momordica charantia, another AMPK activator, is a component of traditional medicines and a novel agent for the treatment of cancer. It is also being evaluated as a nootropic agent.

Areas covered

This article is a comprehensive review which examines the role of AMPK activation in neuroprotection and the role that AMPK activators may have in the management of dementia and cognitive impairment. It evaluates the interaction of metformin, aspirin, and Momordica charantia, with AMPK, and reviews the literature characterizing these agents' impact on neurodegeneration.

Expert opinion

We suggest that AMPK activators should be considered for the treatment and prevention of neurodegenerative diseases. We identify multiple areas of future investigation which may have a profound impact on patients worldwide.

KEYWORDS:

• AMP-activated protein kinases
• aspirin
• cognitive dysfunction
• dementia
• metformin
• momordica charantia
• neurodegenerative diseases

Article Highlights

• Neurodegenerative diseases like dementia exert a profound impact on both individuals and society writ large and their burden of disease is only expected to grow.

• Both metformin and aspirin have been associated with improved cognitive outcomes. These agents are related in their ability to stimulate AMP kinase (AMPK).

• Momordica charantia, a component of traditional medicines used across the world, also activates AMPK and is being evaluated as a neuroprotective agent.

• This article examines the mechanism by which AMPK may be neuroprotective.

• It evaluates the interaction of all three agents, metformin, aspirin, and Momordica charantia, with AMPK, and reviews the literature characterizing their impact on neurodegeneration.

• This article suggests a need for further investigation into the use of AMPK activators to treat and prevent the development of neurodegenerative diseases.

This box summarizes key points contained in the article.

Acknowledgments

The authors would like to acknowledge David Warburton for his critical reading of this paper.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.