Network Analyses Reveal Novel Aspects of ALS Pathogenesis

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Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease causing loss of motor neurons and consequently a progressive deterioration of motor functions. ALS is uniformly fatal with death occurring 5 years after onset of symptoms. There is currently no effective treatment for ALS. Several mutations in a gene called hVAPB have shown that this gene is causative of a type of ALS known as ALS8. In this study we sought to identify genes and cellular processes that are involved in the toxicity conferred by the defective ALS8 allele. By using the power of Drosophila genetics, we performed a large scale genomic screen and identified a number of genes that can affect hVAPB-mediated toxicity. These modifiers cluster into functional pathways known to be involved in ALS as well as novel ones. The relevance of these modifiers and mechanisms for the human disease was confirmed by showing that the human homologues of the fly modifiers can be organized into a network that closely resembles that of the Drosophila genes. Identifying cellular processes and proteins that modulate hVAPB pathological activity can facilitate the discovery of an effective treatment for ALS.

Vyšlo v časopise: Network Analyses Reveal Novel Aspects of ALS Pathogenesis. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005107
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005107

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