The C9ORF72 repeat expansion alters neurodevelopment.
Cell Rep
; 42(8): 112983, 2023 08 29.
Article
en En
| MEDLINE
| ID: mdl-37590144
ABSTRACT
Genetic mutations that cause adult-onset neurodegenerative diseases are often expressed during embryonic stages, but it is unclear whether they alter neurodevelopment and how this might influence disease onset. Here, we show that the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), a repeat expansion in C9ORF72, restricts neural stem cell proliferation and reduces cortical and thalamic size in utero. Surprisingly, a repeat expansion-derived dipeptide repeat protein (DPR) not known to reduce neuronal viability plays a key role in impairing neurodevelopment. Pharmacologically mimicking the effects of the repeat expansion on neurodevelopment increases susceptibility of C9ORF72 mice to motor defects. Thus, the C9ORF72 repeat expansion stunts development of the brain regions prominently affected in C9ORF72 FTD/ALS patients.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Demencia Frontotemporal
/
Proteína C9orf72
/
Esclerosis Amiotrófica Lateral
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2023
Tipo del documento:
Article