Amyloid deposits from different proteins such as TDP-43, C9ORF72 dipeptide repeats (DPRs), phosphorylated high molecular weight neurofilament protein (pNFH), rho guanine nucleotide exchange factor (RGNEF), and FUS have been detected in ALS MNs ( Blokhuis et al., 2013). Protein aggregation is an important feature of ALS pathology. Familial ALS (fALS) accounts for 5–10% of all cases in the United States ( Mehta et al., 2018) involving genes such as superoxide dismutase 1 (SOD1), Chromosome 9 open reading frame 72 (C9ORF72), tar-DNA binding protein 43 (TDP-43), and fused in sarcoma (FUS) ( Chen et al., 2013 Brenner and Weishaupt, 2019). Sporadic forms comprise about 90–95% of all cases. Research studies suggest that multiple phenomena can be involved such as protein misfolding and aggregation, impairment of protein trafficking, oxidative stress, RNA dysmetabolism, failure of protein clearance machinery, and imbalance in protein homeostasis ( Blokhuis et al., 2013 Parakh and Atkin, 2016 Ramesh and Pandey, 2017 McAlary et al., 2019). The exact mechanism of the disease is still unknown. There is no known therapy that can halt the disease. These drugs provide limited relief and slow disease progression by a few months. So far only two drugs are approved by the Federal Drug Administration (FDA) to treat ALS: riluzole and edaravone. Military veterans are approximately twice as likely to develop ALS compared to the average prevalence ( Seals et al., 2016b). Other possible risk factors include genetics, aging, and environmental factors such as toxins, metals, smoking, traumatic head injury, and infections ( Seals et al., 2016a Spencer et al., 2019). Men are at a 1.2 times higher risk to get the disease as compared to women. More than half of all patients do not live more than 3–4 years after diagnosis, 20% live 5 years or more, and only 10% live more than 10 years. The average age of disease onset is 55 years ( Naruse et al., 2019). Ultimately, the breathing muscles are affected leading to respiratory failure ( Borasio and Miller, 2001). ALS patients experience muscle cramps, fasciculations, progressive muscle atrophy and weakness, hyperactive reflexes, difficulty with speech, chewing, and swallowing. It is a progressive and fatal neurodegenerative disease, which affects both upper MNs in the motor cortex and lower MNs in brain stem and the anterior spinal cord ( Ravits and La Spada, 2009). Amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease is the most common motor neuron (MN) disease.
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