Nov 19, 2019

Antisense oligonucleotide therapeutics in neurodegenerative diseases: the case of polyglutamine disorders

Brain : a Journal of Neurology
Ana C SilvaLuis Pereira de Almeida

Abstract

Polyglutamine (polyQ) disorders are a group of nine neurodegenerative diseases that share a common genetic cause, which is an expansion of CAG repeats in the coding region of the causative genes that are otherwise unrelated. The trinucleotide expansion encodes for an expanded polyQ tract in the respective proteins, resulting in toxic gain-of-function and eventually in neurodegeneration. Currently, no disease-modifying therapies are available for this group of disorders. Nevertheless, given their monogenic nature, polyQ disorders are ideal candidates for therapies that target specifically the gene transcripts. Antisense oligonucleotides (ASOs) have been under intense investigation over recent years as gene silencing tools. ASOs are small synthetic single-stranded chains of nucleic acids that target specific RNA transcripts through several mechanisms. ASOs can reduce the levels of mutant proteins by breaking down the targeted transcript, inhibit mRNA translation or alter the maturation of the pre-mRNA via splicing correction. Over the years, chemical optimization of ASO molecules has allowed significant improvement of their pharmacological properties, which has in turn made this class of therapeutics a very promising strategy to ...Continue Reading

  • References169
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Chorionic alpha(2)-microglobulin
MRNA Maturation
Clinic
Genes
Pre-B Lymphocytes
Antistreptolysin O
Nerve Degeneration
Mutant Proteins
Administration Procedure
Protein Biosynthesis

Related Feeds

Antisense Oligonucleotide - Therapies For ALS

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Related Papers

Advanced Drug Delivery Reviews
Melvin M EversWilleke M C van Roon-Mom
Advances in Experimental Medicine and Biology
Morio Ueyama, Yoshitaka Nagai
Nucleic Acids Research
Agnieszka Fiszer, Wlodzimierz J Krzyzosiak
© 2020 Meta ULC. All rights reserved