A ts-paralytic neurodegeneration mutant in Drosophila reveals differential requirement for the glycolytic gene Aldolase in neurons and glia

Abstract

Several neurodegenerative diseases, such as Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease have been linked to metabolic disruption in neurons. This suggests that neurons are particularly sensitive to problems in energy metabolism. However, a controversy currently exists regarding the role of glycolysis in neurons. One hypothesis, the astrocyte-neuron lactate shuttle (ANLS) model, proposes that neurons do not perform their own glycolysis but depend on lactate provided by glial cells as an energy substrate for A TP production. A neurodegeneration mutant in Drosophila melanogaster, known as M4, has been identified and mapped to a small region containing the gene that encodes aldolase. Aldolase is a vital glycolytic enzyme, and a mutation in its coding sequence would likely cause energy deprivation, possibly leading to degeneration of neural tissue and early death. These Drosophila mutants provide a model system to investigate the energy requirements for neuronal viability. To test the ANLS hypothesis, tissue-specific rescue experiments were performed, in which aldolase function was selectively restored to mutants in their neurons and glia individually. The results have shown that, contrary to the ANLS model, neuronal glycolysis is required for viability.