A groundbreaking study conducted by researchers from the Yong Loo Lin School of Medicine at the National University of Singapore (NUS Medicine) has unveiled the potential of a naturally occurring molecule in the human body to restore memory functions in Alzheimer’s disease models. The research, published in the esteemed scientific journal Aging Cell, focuses on the calcium alpha-ketoglutarate (CaAKG), a metabolite deemed safe and previously studied for its role in healthy aging.
A New Approach to Cognitive Aging
Led by Professor Brian K. Kennedy from the Department of Biochemistry and President of the Healthy Longevity Translational Research Program (TRP) at NUS Medicine, the study aimed to assess whether CaAKG could enhance synaptic plasticity, restore memory signals, protect neurons from early degenerative changes, and contribute to healthier cognitive aging. This research represents a shift from traditional strategies that focus solely on the symptoms of specific diseases, like Alzheimer’s, to a geroprotective approach that targets the biology of aging itself. The goal is to reduce the risk or slow the progression of neurodegenerative conditions over time.
Promising Results in Alzheimer’s Models
The findings indicate that CaAKG significantly improved communication between brain cells in Alzheimer’s disease models. It successfully restored associative memory, a cognitive ability often compromised in the early stages of the disease. Researchers emphasize that levels of alpha-ketoglutarate (AKG) naturally decline with age, suggesting that replenishing this metabolite could support the brain’s healthy aging process and mitigate the risk of neurodegenerative diseases.
To delve into how CaAKG operates within the brain, the team examined long-term potentiation (LTP), a crucial process for strengthening neuronal connections and forming lasting memories, which is typically impaired in Alzheimer’s patients. The study demonstrated that CaAKG normalized this essential mechanism. Furthermore, the molecule stimulated autophagy, the brain’s “clean-up” system responsible for removing damaged proteins and maintaining neuronal health, which is another critical factor in protecting against early cellular changes associated with the disease.
A Novel Pathway
The research also identified a new pathway through which CaAKG exerts its effects. According to the study, CaAKG enhances neuronal flexibility by activating L-type calcium channels and calcium-permeable AMPA receptors, bypassing the NMDA receptors usually affected by amyloid accumulation in Alzheimer’s. Additionally, the study highlighted the restoration of synaptic tagging and capture, a fundamental process for linking events and forming associative memories. This suggests that CaAKG could support not only basic memory functions but also more complex forms of learning that deteriorate early in the disease.
These results position CaAKG as a promising candidate for interventions aimed at promoting cognitive health and potentially delaying the onset of Alzheimer’s disease. The discovery of its novel mechanism of action opens new avenues for research and development of treatments that could target the underlying aging processes, rather than just the symptoms of age-related diseases.
The study’s implications are profound, as it not only sheds light on the potential therapeutic benefits of CaAKG but also reinforces the importance of considering the aging process as a whole in the fight against neurodegenerative conditions. With further investigation, CaAKG could become a key player in the arsenal against Alzheimer’s, offering hope for millions affected by this debilitating disease.
Source: Olhar Digital
