Percy Tumbale, of the National Institute of Environmental Health Sciences, National Institutes of Health recently received a Young Investigator Research Award from the National Ataxia Foundation (NAF), to cover her ongoing research on aprataxin mutations in ataxia oculomotor apraxia 1 (AOA1).
Ataxia generally refers to the muscle coordination loss due to the loss, degeneration or damage to nerves cells found in the brain.
Resembling both Friedreich’s ataxia and ataxia-telangiectasia, ataxia oculomotor apraxia 1 is characterized by the symptoms constituting its name; an impaired initiation of saccadic eye movements, difficulties in movement coordination, and neuropathy.
Like several other ataxias, the disease becomes obvious in early childhood. Patients are unable to walk within a decade.
The disease also shares another feature with other ataxias; no treatment is available to prevent progression of AOA1, the condition caused by mutations in the aprataxin gene which codes the protein.
Scientists know that aprataxin is essential for DNA repair mechanisms. It acts as a proofreader for the enzymes and links broken DNA strands in the nuclear genome.
Tumbale is seeking to find if the actions of aprataxin are limited to nuclear DNA repair. Her earlier research showed that mutations in the aprataxin gene are linked to severe symptoms in AOA1 patients but leaves the DNA repair activity of the protein rather intact.
Additionally, because the protein exists in most human tissues but mutations only give rise to neurological disease, there is a possibility that the protein is involved in other processes at fault in AOA1.
The idea is further supported by Tumbale’s research that shows a AOA1-associated mutation in the aprataxin gene that makes the protein leave its location in the nucleolus of the cell without severely impairing the protein activity.
Dr. Tumbale’s NAF-awarded research project will strive to map links between the aprataxin dysfunction and AOA1.
She will pursue two hypotheses: (1) She believes that aprataxin plays important roles in the nucleolus, so that its location to this structure in the cell nucleus is determined by other proteins in the same location. (2) She maintains that Aprataxin mutations in AOA1 block the interactions between the protein and other proteins in the nucleolus, resulting in the movement of aprataxin from this cellular structure, which leaves a dysfunctional nucleolus and contributes to AOA1.
By establishing a molecular platform, Tumbale will expand the current understanding of the physiological role of aprataxind and open up more research that may lead to better diagnostics and interventions for AOA1.