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Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target [RNA-Seq]

ABSTRACT: The study conducted a multiomic analysis of the prefrontal cortex from 51 sporadic ALS patients and 50 control subjects, as well as four transgenic mouse models ( C9orf72, SOD1, TDP-43 and FUS) of ALS with each 5 males/females and 5 case/control samples. The analysis identified sex-specific differences in early disease mechanisms.

ORGANISM(S): Mus musculus

PROVIDER: GSE234245 | GEO | 2024/04/22

REPOSITORIES: GEO

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Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target [miRNA-Seq]

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Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target

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Project description:The past 10 years has seen a rapid acceleration in the discovery of new genetic causes of ALS, with more than 20 putative ALS-causing genes now cited. These genes express proteins that cover a diverse range of molecular functions, including free radical scavenging (cf SOD1), regulation of RNA homeostasis (cf TDP-43, FUS), and protein degradation through the ubiquitin-proteasome system (cf ubiquilin-2, Cyclin F) and autophagy. However, not all of the reported ALS-causing genes have been replicated in subsequent genetic studies – raising significant question marks on the true validity of some putative ALS genes (such as profilin and angiogenin). Furthermore, it still remains unclear what common molecular mechanisms or pathways link these diverse genes/proteins, such that defects in these individual proteins ultimately converge to cause ALS. This study seeks to develop an innovative pipeline to start to address some of these questions.

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RNA Expression Profiling in Lymphoblastoid Cell Lines from Mutated and Non-Mutated Amyotrophic Lateral Sclerosis Patients

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