Details

Autor(en) / Beteiligte

• Haouari, Shanez
• Andres, Christian Robert
• Lanznaster, Debora
• Marouillat, Sylviane
• Brulard, Céline
• Dangoumau, Audrey
• Ung, Devina
• Veyrat-Durebex, Charlotte
• Laumonnier, Frédéric
• Blasco, Hélène
• Couratier, Philippe
• Corcia, Philippe
• Vourc'h, Patrick

Titel

Study of Ubiquitin Pathway Genes in a French Population with Amyotrophic Lateral Sclerosis: Focus on HECW1 Encoding the E3 Ligase NEDL1

Ist Teil von

• International journal of molecular sciences, 2023-01, Vol.24 (2), p.1268

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• The ubiquitin pathway, one of the main actors regulating cell signaling processes and cellular protein homeostasis, is directly involved in the pathophysiology of amyotrophic lateral sclerosis (ALS). We first analyzed, by a next-generation sequencing (NGS) strategy, a series of genes of the ubiquitin pathway in two cohorts of familial and sporadic ALS patients comprising 176 ALS patients. We identified several pathogenic variants in different genes of this ubiquitin pathway already described in ALS, such as , and . Other variants of interest were discovered in new genes studied in this disease, in particular in the gene. We have shown that the HECT E3 ligase called NEDL1, encoded by the gene, is expressed in neurons, mainly in their somas. Its overexpression is associated with increased cell death in vitro and, very interestingly, with the cytoplasmic mislocalization of TDP-43, a major protein involved in ALS. These results give new support for the role of the ubiquitin pathway in ALS, and suggest further studies of the gene and its protein NEDL1 in the pathophysiology of ALS.