Downstream Effects of Mutations in SOD1 and TARDBP Converge on Gene Expression Impairment in Patient-Derived Motor Neurons.

ABSTRACT: Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease marked by death of motor neurons (MNs) present in the spinal cord, brain stem and motor cortex. Despite extensive research, the reason for neurodegeneration is still not understood. To generate novel hypotheses of putative underlying molecular mechanisms, we used human induced pluripotent stem cell (hiPSCs)-derived motor neurons (MNs) from SOD1- and TARDBP (TDP-43 protein)-mutant-ALS patients and healthy controls to perform high-throughput RNA-sequencing (RNA-Seq). An integrated bioinformatics approach was employed to identify differentially expressed genes (DEGs) and key pathways underlying these familial forms of the disease (fALS). In TDP43-ALS, we found dysregulation of transcripts en

SUBMITTER: Dash BP 

PROVIDER: S-EPMC9456253 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature