Disease Mechanisms and Therapeutic Approaches in <i>C9orf72</i> ALS-FTD
A hexanucleotide repeat expansion mutation in the first intron of <i>C9orf72</i> is the most common known genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Since the discovery in 2011, numerous pathogenic mechanisms, including both loss and gain of function, hav...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/9/6/601 |
| Summary: | A hexanucleotide repeat expansion mutation in the first intron of <i>C9orf72</i> is the most common known genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Since the discovery in 2011, numerous pathogenic mechanisms, including both loss and gain of function, have been proposed. The body of work overall suggests that toxic gain of function arising from bidirectionally transcribed repeat RNA is likely to be the primary driver of disease. In this review, we outline the key pathogenic mechanisms that have been proposed to date and discuss some of the novel therapeutic approaches currently in development. |
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| ISSN: | 2227-9059 |