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SOD1 binds copper and zinc ions and is one of three superoxide dismutases responsible for destroying free superoxide radicals in the body. The encoded isozyme is a soluble cytoplasmic and mitochondrial intermembrane space protein, acting as a homodimer to convert naturally occurring, but harmful, superoxide radicals to molecular oxygen and hydrogen peroxide.
A 2016 paper proposed that SOD1 maturation and proteins regulating intracellular copper levels are potential therapeutic targets of SOD1-ALS. [27] The DNA oxidation product 8-oxoG is a well-established marker of oxidative DNA damage. 8-oxoG accumulates in the mitochondria of spinal motor neurons of persons with ALS. [32]
Mutations in SOD1 can cause familial ALS (several pieces of evidence also show that wild-type SOD1, under conditions of cellular stress, is implicated in a significant fraction of sporadic ALS cases, which represent 90% of ALS patients.), [45] by a mechanism that is presently not understood, but not due to loss of enzymatic activity or a ...
Tofersen, sold under the brand name Qalsody, is a medication used for the treatment of amyotrophic lateral sclerosis (ALS). [2] Tofersen is an antisense oligonucleotide that targets the production of superoxide dismutase 1, an enzyme whose mutant form is commonly associated with amyotrophic lateral sclerosis.
About 95% of ALS patients have abnormalities in the nucleus-cytoplasmic localization in spinal motor neurons of TDP43. In TDP-43 depleted human neural stem cell-derived motor neurons, as well as in sporadic ALS patients' spinal cord specimens there is significant double-strand break accumulation and reduced levels of NHEJ.
ALS is the most common form of the motor neuron diseases. [8] ALS often presents in its early stages with gradual muscle stiffness, twitches, weakness, and wasting. [3] Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost. [3]
The Center was opened in addition to the continual operation of three research laboratories and the Lois Insolia ALS Clinic. [10] Among the Center's contributions to ALS research have been the 1993 co-discovery of the first genetic mutation linked to cause ALS, SOD1, [11] [12] as well as FUS in 2009 [13] [14] and others linked to familial ALS.
The structure of domain II greatly resembles that of SOD1 which allows it to perform the function of binding to SOD1. [5] Domain III contains a CXC Cu binding motif and performs the Cu insertion and subsequent disulfide oxidation of SOD1. [5] When CCS docks to SOD1, cysteine 244 of CCS and 57 of SOD1 form a disulfide linkage. [6]