Published April 16, 2020
Jacobs School of Medicine and Biomedical Sciences researchers are seeking to improve understanding of the glial maintenance and support of axons — the very long cellular projections of neurons relaying electrical and biochemical signals in nerves and white-matter tracts of the nervous system.
Bogdan K. Beirowski, MD, PhD, assistant professor of biochemistry, and Elisabetta Babetto, PhD, senior research scientist in biochemistry and research assistant professor of pharmacology and toxicology, are leading the study.
As investigators at the Hunter James Kelly Research Institute, they have been awarded a five-year, $1.9 million grant from the National Institute of Neurological Disorders and Stroke for their study titled “Elucidating the Trophic Support of Long Axons by Metabolic Signaling in Oligodendrocytes.”
Axons are critical for neuronal wiring and transport of neuronal maintenance signals. They constitute the largest part of the neuron. However, because of their incredible length, axons are extremely vulnerable.
Axon degeneration (AxD) is a hallmark of many neurodegenerative conditions such as Alzheimer’s disease and multiple sclerosis, and occurs very early in these conditions and leads to irreversible symptoms.
“Therefore it is essential to understand the underlying molecular and cellular mechanisms in hope of tailoring specific neuroprotective strategies that ameliorate the disease,” Beirowski says. “Importantly, a growing body of evidence suggests that oligodendrocytes (OLGs), the axon-flanking glia in the central nervous system, provide essential metabolic support to long axons.”
“Recent studies have shown that metabolic abnormalities in oligodendrocytes can evoke axon degeneration. This could be germane to axon degeneration in neurodegenerative diseases.”
“My group recently discovered that the liver kinase B1 (LKB1) pathway regulates many metabolic components in oligodendrocytes, which are central to the support of axons,” Beirowski says. “Mutant mice in which the LKB1 pathway is inactivated display progressive degeneration of axons, thus modeling AxD in disease. In the grant, we intend to study as to how the glial LKB1 pathway promotes axon stability.”
Specific aims of the study are to:
“The degeneration of long axons is a common and unifying feature of many neurodegenerative conditions, not only classical neurological disorders, but also epidemiologically important diseases such as glaucoma and diabetic neuropathy,” Beirowski says.
“It is recognized that axon degeneration results in the most relevant symptoms in many of these diseases,” he adds. “If we can find novel therapeutic approaches to specifically protect axons and therefore alleviate the symptoms in these ailments, this would have wide-reaching public health impact.”
Selva Baltan, MD, PhD, of the Oregon Health & Science University School of Medicine is also a collaborator on the grant.