Agmatine as a novel intervention for Alzheimer's disease: Pathological insights and cognitive benefits

• Published in: Ageing research reviews Vol. 96; p. 102269
• Main Authors: Katariya, Raj A., Sammeta, Shivkumar S., Kale, Mayur B., Kotagale, Nandkishor R., Umekar, Milind J., Taksande, Brijesh G.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.04.2024
• Subjects: Agmatine; Alzheimer's disease; Amyloid beta; L-arginine; Amyloid beta; Alzheimer's disease; Agmatine; L-arginine
• ISSN: 1568-1637; 1872-9649; 1872-9649
• DOI: 10.1016/j.arr.2024.102269

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and a significant societal burden. Despite extensive research and efforts of the multidisciplinary scientific community, to date, there is no cure for this debilitating disease. Moreover, the existing pharmacotherapy for AD only provides symptomatic support and does not modify the course of the illness or halt the disease progression. This is a significant limitation as the underlying pathology of the disease continues to progress leading to the deterioration of cognitive functions over time. In this milieu, there is a growing need for the development of new and more efficacious treatments for AD. Agmatine, a naturally occurring molecule derived from L-arginine, has emerged as a potential therapeutic agent for AD. Besides this, agmatine has been shown to modulate amyloid beta (Aβ) production, aggregation, and clearance, key processes implicated in AD pathogenesis. It also exerts neuroprotective effects, modulates neurotransmitter systems, enhances synaptic plasticity, and stimulates neurogenesis. Furthermore, preclinical and clinical studies have provided evidence supporting the cognition-enhancing effects of agmatine in AD. Therefore, this review article explores the promising role of agmatine in AD pathology and cognitive function. However, several limitations and challenges exist, including the need for large-scale clinical trials, optimal dosing, and treatment duration. Future research should focus on mechanistic investigations, biomarker studies, and personalized medicine approaches to fully understand and optimize the therapeutic potential of agmatine. Augmenting the use of agmatine may offer a novel approach to address the unmet medical need in AD and provide cognitive enhancement and disease modification for individuals affected by this disease. [Display omitted] •Agmatine regulates pivotal processes in AD pathogenesis, including the production, aggregation, and clearance of Aβ.•It exerts neuroprotective effect, modulates neurotransmitters, enhances synaptic plasticity and stimulates neurogenesis.•·It enhances learning and cognition and also improve other neuropsychiatric complications in AD.•Agmatine may offer a new therapeutic approach to address the unmet medical need in AD.