The mutant form of the Huntington gene, mHTT, which encodes a product that causes the disease, is expressed throughout the brain in affected individuals. Yet neurons in individual regions of the brain are differentially susceptible to its neurotoxic effects. The basis for this puzzling region-specific vulnerability in Huntington disease—which is likewise a feature of Alzheimer and Parkinson neurodegenerative diseases—was hitherto unknown.
A new study led by Cynthia McMurray, a senior scientist in Molecular Biophysics and Integrated Bioimaging (MBIB), provides evidence that regional differences in neuronal susceptibility to Huntington disease can be attributed to substrate-driven metabolic reprogramming strategies adopted by astrocytes in response to low glucose. The team recently reported their findings in the journal Cell Metabolism.