Identified Potential Causes of Amyotrophic Lateral Sclerosis and Related Possible Treatments

Identified potential causes of Amyotrophic Lateral Sclerosis and related possible treatments.

Amyotrophic Lateral Sclerosis (ALS) is a neurological disease that targets motor neurons (nerve cells that are responsible for voluntary skeletal muscle movement). The disease is fatal and causes rapid paralysis due to the degeneration of these neurons, and currently has no definitive treatment – largely because its specific cause is unknown. Cirulli et al.  identified many of the genes that may have a direct or indirect link to ALS development, and Wu et al. (2012) further emphasised the role of the specific gene Profilin1, and its associated proteins and damage in the onset of ALS. Kang et al. described how ALS will cause deterioration of oligodendrocytes, which are essential cells that help nourish neurons and increase the speed of their conduction, hence in turn causing the degeneration of the neurons themselves. Bede et al. (2013) showed a deterioration of the basal ganglia (a group of areas of the brain serving multiple functions) caused by the progression of ALS, and which further contributes to impaired function. Finally, based on some identified causes, Pandya et al. (2013) identified a number of potential treatment options for ALS. This annotated bibliography will discuss a number of the factors linked to ALS onset and its associated symtoms; as well as how those can direct research for potential treatments.

Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

Genetic makeup is known to play a role in the development of ALS, but the specific genes involved are still unknown. This primary article aimed to identify some of the genes that may be linked with ALS, and determine how they operate. The study used whole-exome sequencing of 2869 ALS patients as well as many controls without ALS in order to identify common genetic patterns amongst them that did not appear in the controls. (Exome sequencing involves only the genes that will be transcribed into proteins). The article found several genes indirectly involved in the disease and one gene, TBK1 which seemed to show a direct link to ALS. The study concludes to state that the identification of the genes is a promising step towards new treatments for ALS.

Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis

This primary article demonstrated a relationship between a mutation on the Profilin 1 gene, and the development of familial ALS (ie ALS that is inherited). This gene is known to have an important role in the conversion of actin, which is in turn important for muscle contraction and thus movement. Exome sequencing was performed (whereby only genes which have an actual function were identified) to test for the presence of the Profilin1 mutation in ALS patients. 4 different mutations were identified within the gene. Furthermore, many of those mutations were also found to encode an established ALS-linked protein (TDP-43). These mutations were also shown to cause decreased actin amounts and less axon growth (a crucial structure within neurons).