Alternative Splicing of ALS Genes: Misregulation and Potential Therapies

Cellular and Molecular Neurobiology
Benedetta PerroneSebastiano Cavallaro

Abstract

Neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Parkinson's, Alzheimer's, and Huntington's disease affect a rapidly increasing population worldwide. Although common pathogenic mechanisms have been identified (e.g., protein aggregation or dysfunction, immune response alteration and axonal degeneration), the molecular events underlying timing, dosage, expression, and location of RNA molecules are still not fully elucidated. In particular, the alternative splicing (AS) mechanism is a crucial player in RNA processing and represents a fundamental determinant for brain development, as well as for the physiological functions of neuronal circuits. Although in recent years our knowledge of AS events has increased substantially, deciphering the molecular interconnections between splicing and ALS remains a complex task and still requires considerable efforts. In the present review, we will summarize the current scientific evidence outlining the involvement of AS in the pathogenic processes of ALS. We will also focus on recent insights concerning the tuning of splicing mechanisms by epigenomic and epi-transcriptomic regulation, providing an overview of the available genomic technologi...Continue Reading

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Citations

Nov 16, 2019·Orphanet Journal of Rare Diseases·Antonia AssuntoDaniela Melis
Jun 4, 2020·Phytotherapy Research : PTR·Milad AshrafizadehKwang Seok Ahn
Jul 9, 2020·Medicinal Research Reviews·Maria Zakharova
Feb 18, 2020·Neuropharmacology·Adriano ChiòGabriele Mora
Jan 18, 2021·The Journal of Biological Chemistry·Dan WuYun Stone Shi
May 22, 2021·Translational Neurodegeneration·Dunhui LiMay Thandar Aung-Htut
Aug 28, 2021·Genes·Eglė Jakubauskienė, Arvydas Kanopka

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Methods Mentioned

BETA
ISSs
exome sequencing
RNAseq
antisense oligonucleotides
SMA
antisense oligonucleotide

Clinical Trials Mentioned

NCT01041222
NCT02623699
NCT03626012

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