Disrupted Glucose Metabolism in Huntington’s Disease Explored in New Study

Disrupted Glucose Metabolism in Huntington’s Disease Explored in New Study

Researchers from the Weill Cornell Medical College Brain and Mind Research Institute in White Plains, New York are studying Huntington’s disease by exploring biochemical pathways in mouse models of the disease. The team, led by Nima N. Naseri in the laboratory of Gary E. Gibson, PhD, found that an abnormal tricarboxylic acid cycle in Huntington Disease patients’ brains leads to abnormal glucose metabolism, and they searched to find the answer as to how.

Publishing their findings in the¬†Journal of Neuropathology & Experimental Neurology, the team presented their theories in the article, “Abnormalities in the Tricarboxylic Acid Cycle in Huntington Disease and in a Huntington Disease Mouse Model.” Through a series of carefully planned experiments, the team found that mitochondrial enzymes were causing problems in glucose metabolism. These enzymes included pyruvate dehydrogenase complex and those found in the tricarboxylic acid cycle.

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Between mouse models and human data collected from brains, the team found that enzymatic activity was significantly lower (50% to 90% lower) in humans than in mice, with the exception of succinate dehydrogenase, which was 35% in the human cortex and 23% in the mouse cortex. Additionally, other key enzymes, such as isocitrate dehydrogenase and succinyl thiokinase, showed an increase in transcription from DNA to mRNA. Synthesizing more of these enzymes may be a mechanism used by the body to revert back to a normal state.

Despite the discrepancies, using mouse models of Huntington’s disease is valuable to developing new treatments for the disease. “These patterns of change differ from those reported in other diseases, which may offer unique metabolic therapeutic opportunities for HD patients,” wrote the authors. What drugs may not work in other patients with mitochondrial disorders or other metabolic diseases may work in individuals with Huntington’s disease.

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