Amyotrophic Lateral Sclerosis, more formally known as ALS or Lou Gehrig’s disease, is a neurodegenerative disease, causing the selective degeneration of both upper and lower motor neurons, as well as those in the motor cortex portion of the brain, which ultimately leads to the limited to complete loss of all voluntary muscle function. Now while the main pathology of ALS is the selective death of the previously mentioned motor neurons, more recent studies have suggested that the homeostatic imbalance of the whole body or just key cellular metabolism may help to increase the rate of progression of the disease. Sadly none-the-less this occurrence is one that proves to be ultimately fatal, generally resulting in death within three to five years
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They did studies into whether the SOD1 mutant could cause amyloid fibrils, under normal physiological conditions. You may be wondering what this has to do with fALS, well quite basically amyloid fibrils are extremely strong, highly ordered and destructive fibrils that accumulate in tissues and assist in the progression of neurodegenerative diseases, such as Alzheimer’s or Parkinson’s disease. The focus of the research was to mainly understand the structural basis for the formation of amyloid fibrils from the SOD1 mutant. Results we compared to both Sporadic and Familial ALS studies. What was found was if the metal, that is the Copper (Cu) and Zinc (Zn) which make up the structural bases of the SOD1 mutant, were removed, the structures of both Sporadic and Familial ALS were destabilized dramatically. (Masataka Ida, …show more content…
In the Sporadic form of the disease it was found to remarkably decrease the structural stability of the mutant SOD1, but from these disulfide reduced proteins amyloid fibrils were formed in vivo, meaning within living subjects. This clearly indicated that the natural reduction of the intramolecular disulfide bonds was the deciding factor in the formation of the destructive amyloid fibrils. (Masataka Ida, 2015)
Experiments done by the Musaro group was done on the expression of the SOD1 mutant in skeletal muscle as it directly contributes to the pathological development of ALS. The studies showed that selective expression caused pathological alterations to the disease, including pre-symptomatic signs of ALS. The studies also formally proved that muscle atrophy isn’t determined by motor neuron degeneration, and that skeletal muscle is a direct contributor to the ALS pathogenesis. All this suggest that the skeletal muscle is to be considered as a primary target of the SOD1
They did studies into whether the SOD1 mutant could cause amyloid fibrils, under normal physiological conditions. You may be wondering what this has to do with fALS, well quite basically amyloid fibrils are extremely strong, highly ordered and destructive fibrils that accumulate in tissues and assist in the progression of neurodegenerative diseases, such as Alzheimer’s or Parkinson’s disease. The focus of the research was to mainly understand the structural basis for the formation of amyloid fibrils from the SOD1 mutant. Results we compared to both Sporadic and Familial ALS studies. What was found was if the metal, that is the Copper (Cu) and Zinc (Zn) which make up the structural bases of the SOD1 mutant, were removed, the structures of both Sporadic and Familial ALS were destabilized dramatically. (Masataka Ida, …show more content…
In the Sporadic form of the disease it was found to remarkably decrease the structural stability of the mutant SOD1, but from these disulfide reduced proteins amyloid fibrils were formed in vivo, meaning within living subjects. This clearly indicated that the natural reduction of the intramolecular disulfide bonds was the deciding factor in the formation of the destructive amyloid fibrils. (Masataka Ida, 2015)
Experiments done by the Musaro group was done on the expression of the SOD1 mutant in skeletal muscle as it directly contributes to the pathological development of ALS. The studies showed that selective expression caused pathological alterations to the disease, including pre-symptomatic signs of ALS. The studies also formally proved that muscle atrophy isn’t determined by motor neuron degeneration, and that skeletal muscle is a direct contributor to the ALS pathogenesis. All this suggest that the skeletal muscle is to be considered as a primary target of the SOD1