Chromosome 9p21.2 and Amyotrophic Lateral Sclerosis: A causal pathogenic link?
Dorland, R. van
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In this thesis we discussed the function and possible role of IFT-74, Tie2, C9orf14, C9orf11, MOBKL2B, IFNK, C9orf72 and LINGO2 in the pathogenesis of ALS. Some of these genes (IFT-74, Tie2, MOBKL2B, IFNK and LINGO2) have great potential in playing a causal role in the development of ALS. Thus far, IFT-74 is the only gene in this region in which mutations in fALS patients have been found. Its function in axonal transport, a crucial process for neurons, strengthens the idea of this protein being causally linked to the development of ALS even more. Tie2, IFNK and LINGO2 all have one common trait in that they are thought to influence neuronal survival via the PI3K/Akt pathway. This pathway is an important regulator of neuronal cell death and this suggests a possible role of these proteins in the pathogenesis of ALS. Future research should focus on determining the level of expression of these promising genes in sALS and fALS patients. Also, mutational screening in sALS patients can contribute to a better understanding of the possible role of these candidate genes in the pathogenesis of ALS.