New Insights into Neuronal Metabolism and Their Role in Neurodegeneration Resistance

Recent research from the University of Michigan has shed light on how metabolic signals within neurons influence their fate following injury or disease. Unlike most body cells, neurons are rarely replaced after damage, and their axons—the long projections that transmit electrical signals—tend to degrade rather than regenerate, contributing to neurodegenerative processes. However, this new study suggests that the way neurons process sugar, fundamentally tied to their metabolism, plays a critical role in determining whether they succumb to degeneration or resist it.

The investigation, published in the journal Molecular Metabolism, used a fruit fly model to explore these mechanisms, supported by agencies such as the NIH and NSF. The findings reveal that reducing neuronal sugar metabolism can compromise neural integrity, while in injured neurons, this modulation can activate protective pathways that help prolong axon survival.

Central to this process are two proteins: DLK (dual leucine zipper kinase), which detects neuronal injury and becomes activated by disrupted metabolism, and SARM1, involved in axon degeneration and closely linked with DLK activity. The study demonstrated that when neurons have healthy metabolic signaling, DLK activity maintains axonal integrity and suppresses SARM1-driven degeneration. Conversely, prolonged activation of DLK can paradoxically accelerate neurodegeneration, highlighting the complex dual roles these signals play.

The researchers emphasize that targeting DLK’s activity for therapeutic purposes must be approached with caution, given its dual protective and harmful effects. Understanding how metabolic signals influence these proteins could pave the way for novel treatments aimed at delaying or preventing neurodegenerative diseases, such as Alzheimer's and stroke-related injuries.

In essence, the study proposes that neuronal metabolism does more than support energy needs—it actively shapes the cell’s response to injury. By fine-tuning these metabolic pathways, future strategies might enhance the natural resilience of neurons, providing new hope for combating neurodegeneration and neurological decline.