Explored Role of Enriched Glutamate Homeostasis in Oculomotor Evasion of Amyotrophic Lateral Sclerosis (ALS) using Geo2R Analysis


Topic:

What’s New in ALS and CMT - molecular pathways, mutations, phenotype-genotype correlations

Poster Number: 213

Author(s):

Aayan Patel

Institutions:

1. University of Nevada, Reno

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that causes death and compromised function of motor neurons. There is little known about the underlying mechanisms the disease uses to cause neurodegeneration and as a result, effective treatment is difficult. However, it is well known that oculomotor neurons are able to avoid ALS onset and function relatively normally compared to other motor neurons in diseased patients. In order to explore why oculomotor neurons aren’t affected in ALS patients, this study uses GEO2R analysis and Gene Ontology to compare gene expression profiles of datasets GSE 40438 and GSE 833. GSE 40438 compares gene expression profiles of oculomotor neurons and lumbar spinal neurons in healthy patients. GSE 833 compares gene expression profiles of spinal neurons from healthy and ALS-affected patients. Through meta-analysis and Volcano Plot construction with R, this study finds that oculomotor neurons overexpress GAD2, GABRE, and CALB1 relative to lumbar spinal neurons. Utilizing STRING and the KEGG pathway database, all three genes facilitate preventative measures against excitotoxicity (glutamate toxicity), a hypothesized cause of ALS. This enriched function is heavily underexpressed in ALS-affected spinal neurons compared to healthy spinal neurons, signifying that natural oculomotor upregulation may be a protective mechanism against ALS. Such a finding provides support for the excitotoxicity-induced ALS hypothesis and generates insight about a key pathway that could be targeted to prevent or cure ALS.