Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease and motor neurone disease (MND), is a fatal disorder of motor neurons. It is the most common adult-onset motor neuron disease and is characterized by progressive paralysis and death. Currently, no treatment substantially slows disease progression. The etiological underpinnings of ALS are complex and not fully understood. A lot of genes have been implicated in ALS, including C9orf72, SOD1, TARDBP, and FUS, which are key to the normal function of motor neurons and other cells.
Now a new study shows that a variant in UBQLN4 gene is associated with ALS. The study, led by Dr Yongchao Ma from Northwestern University Feinberg School of Medicine, reveals that UBQLN4 gene variant disrupts a pathway that drives motor neuron development.
Previous studies suggest that mutations in UBQLN4 gene can trigger ALS and ALS/dementia in humans. In the current study, Dr Ma and colleagues screened the UBQLN family of genes in patients with familial ALS and identified a novel variant in UBQLN4 that is associated with ALS. They further demonstrated that the UBQLN4 gene variant impairs a pathway involved in breaking down a protein called beta catenin, leading to the buildup of the protein. This, in turn, impairs motor neuron structure.
When the researchers used a drug to inhibit beta-catenin function in a Zebrafish model, the defects in motor neurons caused by the UBQLN4 gene variant were reversed. The drug, called quercetin, is a flavonol found in many plants, used as an ingredient in supplements, and has been promoted for the treatment of many human diseases including cancer.
Collectively, the findings indicate that inhibition of beta-catenin function may a treatment strategy for patients with ALS who have the the UBQLN4 variant. “These findings provide a strong link between the regulation of axonal morphogenesis and a new ALS-associated gene variant mediated by protein degradation pathways,” the researchers concluded. The findings, if confirmed, may lead to new therapies for this devastating degenerative disease.
The study “A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis” is described in the journal eLife. (Cusabio offers Recombinant ITGB6.)
留言列表
