According to a new study, published in Cell Reports, researchers have highlighted the molecular responses that trigger an inherited movement and neurodegenerative condition known as ARSACS – Autosomal recessive spastic ataxia of Charlevoix-Saguenay, named after two Quebec valleys as the initial cases were discovered there. Children suffering from ARSACS mostly have difficulty in walking in the second year of life and many other neurological issues in the later years. In the cerebellum – a part of the brain responsible for coordinating movement and balance, neurons called Purkinje cells get damaged in children with ARSACS. In most cases, people are on a wheelchair by their 30s-40s, and have a shorter lifespan.
The movement disorder is caused because of the mutation and functional loss of a gene, named SACS, which handles a very huge protein called sacsin, which has been difficult to study individually or in part because of its big size. Comparatively, very little has been known about its normal functions, and how a missing protein can cause this disease.
Study co-senior author Justin Wolter, PhD, a postdoctoral researcher at the UNC Neuroscience Center, said, "We tried to take an unbiased approach to understand what goes wrong when cells lose sacsin. Our results suggest that the death of Purkinje cells in ARSACS may possibly result from changes in neuronal connectivity and synaptic structure." Another co-senior author of the study was Paul Chapple, PhD, a professor of molecular cell biology at Queen Mary University of London.
Chapple said, "There appear to be multiple overlaps between ARSACS and other brain disorders." Wolter said, "We showed for example that there’s disruption of tau biology in cells lacking sacsin, and of course abnormalities in tau are also a well-known feature of Alzheimer’s disease. So we think studying this rare neurological condition could provide insights into much more common ones. Much work remains to be done to understand the mechanisms by which synaptic connectivity is affected and whether it is contributing to neuronal death. But, if it is, it could inform future therapeutic approaches."