Reactivating Mitochondria to Treat Alzheimer’s Disease
A study conducted by researchers at the Scripps Institute, published in the journal “Science Advances,” identified the dysregulated active reactions in brain cells that contribute to neuronal decline in Alzheimer‘s disease.
Researchers discovered a disrupted enzyme, “SNO,” resulting from abnormal nitrogen and oxygen atoms attached to the sulfur atom, a process known as “S-nitrosylation.” This reaction was observed in Alzheimer‘s-afflicted brain neurons, leading to the disruption of the Krebs cycle in mitochondria, crucial for cellular energy production.
The Krebs cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle, is a fundamental metabolic pathway occurring within mitochondria in nucleated cells, including those in the human body. This cycle is a vital part of cellular respiration, where cells generate energy in the form of adenosine triphosphate (ATP).
Using human neuronal cells derived from Alzheimer‘s patient stem cells, researchers employed a small molecule to rectify mitochondrial dysfunction, restoring numerous connections between nerve cells. The study highlights the potential of improving mitochondrial metabolism as a therapeutic target for Alzheimer‘s disease and associated disorders.
Researchers pinpointed a bottleneck in the Krebs cycle involving the molecule succinate, which inhibits energy production. By providing the missing succinate molecules, they succeeded in restoring lost neuronal connections in neuronal cell models.
While the study demonstrates proof of concept in reactivating the Krebs cycle in live neuronal cells derived from Alzheimer‘s patients, researchers emphasize the need for better compounds before developing an effective drug for humans.
The aim is to find a safe and effective drug to sustain energy and restore neuronal connectivity in Alzheimer‘s patients, potentially halting disease progression and enhancing cognitive function.
The research team, led by senior author Stuart Leibson, will continue to explore the Krebs cycle in mitochondria as a promising therapeutic target for Alzheimer‘s disease.
