![]() By Bryce Miller Sophomore, Biochemistry Major Mississippi State University
In humans, the ATXN1 gene codes for the protein ataxin-1, whose function is not fully known.
The SCA1 is a repeat expansion disease, meaning a part of the DNA made up of building blocks cytosine, adenine, and guanine, referred to as CAG nucleotide repeat, occurs multiple times in the ATXN 1 gene. The CAG trinucleotide repeat on the ATXN 1 gene triggers the SCA1 disorder. The codon CAG codes for the amino acid glutamine abbreviated Q. Therefore, SCA1 is also called a polyglutamine or poly Q disorder. In SCA1, ATXN1 alleles can carry 39–81 CAG repeats. The CAG trinucleotide in ATXN 1 gene results in excessive glutamine in the ataxin-1 protein. The extra glutamine increases the length of the protein, which causes it to misfold. The misfolded ataxin-1 protein forms clumps or aggregates with other proteins preventing ataxin-1 from performing its normal function and cell death. The cells in the cerebellum, the part of the brain that coordinates movement, are susceptible to changes in ataxin-1 function leading to SCA1. What are the Symptoms and Signs of SCA1? The symptoms of SCA 1 develop in the mid-thirties and rarely in early childhood or late in life. Patients start showing problems with walking and coordinating hand movements. Unsteady gait, limping, and poor coordination in various body parts are common during the disease's initial stages. Patients have trouble expressing their thoughts due to slurred speech. Patients with SCA1 can have dysphagia, or difficulty swallowing, increasing the risk of choking while eating and drinking. Eye movement can also be affected, causing eyes not to focus or move to their desired location quickly. All of these symptoms result from the degeneration of the cerebellum. How is SCA1 Diagnosed? Current diagnostic methods employ blood tests, imaging studies through MRI, lumbar puncture or spinal tap, and molecular genetic testing. Molecular genetic testing can identify SCA1 cases accurately. Patients who have ATXN 1 alleles with 39 or more CAG trinucleotide repeats are 100% affected by SCA1 . An MRI of the brain can show cerebellar shrinkage in patients with ataxia. Treatment and Management There is no treatment for SCA1 yet. As SCA1 is a monogenic disease, current strategies target the ATXN1 gene. A study using conditional transgenic mouse model of SCA1 showed that preventing mutant ATXN1 expression during the initial phase of the disease results in improved coordination and motor activities. Another study in SCA 1 mice showed that RNA Interference by shRNAs and siRNAs targeting mutant ATXN1 led to a reduction in the ATXN1 inclusions, restored cerebellar morphology, and improved motor function. Antisense oligonucleotides targeting ATXN1 RNA expression has shown promising results in mouse models of SCA1. Comments are closed.
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