“`html
Discoveries may yield fresh avenues for treating and exploring neurodegenerative disorders
In contrast to the majority of cells in the human organism, neurons—the active components of our nervous system—typically cannot replicate themselves with healthy versions after experiencing damage.
Instead, following an injury caused by events like a stroke, concussion, or neurodegenerative disorder, neurons and their axons, slender projections that transmit electrical signals, are significantly more prone to deterioration than recovery.
However, recent investigations from the University of Michigan introduce innovative perspectives on neurodegeneration that may assist in shielding patients from such deterioration and cognitive decline in the future. The publication, found in the journal Molecular Metabolism, could even bring us closer to grasping the infrequent instances in which brain repair occurs and pave new avenues for treatment development, according to the researchers.
Their results, derived from a well-established fruit fly model, imply that the resilience of neurons against degradation is linked to the core mechanism of how these cells process glucose. This research was supported by the National Institutes of Health, the U.S. National Science Foundation, the Rita Allen Foundation, and the Klingenstein Fellowship in the Neurosciences.
“Metabolism is frequently altered in brain injuries and conditions such as Alzheimer’s, yet we remain uncertain whether this is a cause or a consequence of the illness,” stated senior author Monica Dus, a U-M associate professor of molecular, cellular, and developmental biology.
“Here we discovered that reducing sugar metabolism compromises neural integrity, but if the neurons are already compromised, the same adjustment can preemptively initiate a protective response. Rather than deteriorating, axons persist for a longer duration.”
Postdoctoral research fellow TJ Waller, who led the study, found that two specific proteins seem to play a role in prolonging the health of axons. One of these is known as dual leucine zipper kinase, or DLK, which detects neuronal injury and is triggered by impaired metabolism. The other protein is referred to as SARM1—abbreviated from Sterile Alpha and TIR Motif-containing 1—associated with axon degeneration and linked to the DLK response.
“What astonished us is that the neuroprotective response varies based on the cell’s internal environment,” Dus mentioned. “Metabolic indicators influence whether neurons maintain their integrity or begin to degenerate.”
Typically, in situations where neurons and axons remain intact, DLK becomes increasingly active and the movement of SARM1 is limited. However, there are complexities. In fact, sustained DLK activation over time results in progressive neurodegeneration, as demonstrated by the study, effectively negating earlier neuroprotective effects.
DLK, in particular, has surfaced as a focal point for researching and treating neurodegenerative diseases. Yet, researchers will face technical hurdles in managing DLK’s dual detrimental and beneficial properties, Waller noted.
“If we aim to postpone disease progression, we must inhibit its adverse aspects,” Waller explained. “We want to ensure that we are not impeding the positive aspects that might actually contribute to naturally decelerating the disease.”
Understanding the dual functionality of a molecule like DLK presents a challenging enigma that researchers have yet to unravel. Deciphering the mechanisms by which modulators like DLK transition between protective and detrimental states could have significant implications for addressing neurodegenerative disorders and brain injuries, directly impacting clinical populations.
Dus and Waller emphasized that comprehending this mechanism “offers a fresh outlook on injury and disease, one that transcends merely blocking damage to focusing on what the system is already doing to fortify itself.”
“`