Amyotrophic lateral sclerosis (ALS) is the most prevalent neuromuscular disease worldwide. It is a lethal and progressive neurodegenerative disease, principally affecting motor neurons; patient clinical characteristics are muscle weakness, dysphagia and respiratory failure. The mean age is related to family history (40 years, familial ALS or FALS) or with no family history (50 years), but it is more common in people aged 60–69 years.
The cause of ALS is not known and it is not known yet why it affects some people and not others. However expert consensus is that molecular alterations in different cells are involved in the development and progression of the disease. For example, motor neuron death is caused by a variety of cellular defects, including the processing of RNA molecules, water channels, and calcium levels, increasing evidence that these alterations of cells in the nervous system play an important role in ALS.
Here we will systematically examine different genes (AQP1, SLC14A1, MT1X, DSCR1L1, PCP4, UCHL1, GABRA1, EGR1, OLFM1 and VSNL1) that are “up or down” regulated in the motor cortex and spinal cord and their association with ALS risk. These could be novel biomarkers associated with ALS risk.
We built an interaction Network with Cytoscape, this was used to identify pathways, miRNA and drugs associated to ALS. The most important affected pathway is PI3K-Akt signaling. Thirteen microRNAs (miRNA-19B1, miRNA-107, miRNA-124-1, miRNA-124-2, miRNA-9-2, miRNA-29A, miRNA-9-3, miRNA-328, miRNA-19B2, miRNA-29B2, miRNA-124-3, miRNA-15A and miRNA-9-1) and four drugs (Estradiol, Acetaminophen, Progesterone and resveratrol) for new possible treatments were identified.Graphical abstract:
Proposed model of neurodegeneration in SALS for ten genes analyzed in this review, we show the possible mechanisms associated with the damage, for example increase in oxidative stress, abnormal calcium homeostasis among other.