Titre :

Effects of the therapeutic correction of U1 snRNP complex on Alzheimer's disease

Auteur(s) :

Leal, Caio Bruno Q. S. [Auteur]
Zimmer, Camila G. M. [Auteur]
Sinatti, Vanessa V. C. [Auteur]
Soares, Ericks S. [Auteur]
Poppe, Britt [Auteur]
De Wiart, Adrien Carton [Auteur]
Chua, Xue Ying [Auteur]
Da Silva, Ronan V. [Auteur]
Magdesian, Margaret H. [Auteur]
Rafii, Michael S. [Auteur]
Buee, Luc [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Bottos, Rafael M. [Auteur]

Titre de la revue :

Scientific Reports

Nom court de la revue :

Sci Rep

Numéro :

14

Date de publication :

2024-12-03

ISSN :

2045-2322

Mot(s)-clé(s) en anglais :

Alzheimer's disease
Astrogliosis
TAU
Amyloid-beta
U1-70K
U1 snRNP

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

The U1 snRNP complex recognizes pre-mRNA splicing sites in the early stages of spliceosome assembly and suppresses premature cleavage and polyadenylation. Its dysfunction may precede Alzheimer’s disease (AD) hallmarks. ...
Lire la suite >The U1 snRNP complex recognizes pre-mRNA splicing sites in the early stages of spliceosome assembly and suppresses premature cleavage and polyadenylation. Its dysfunction may precede Alzheimer’s disease (AD) hallmarks. Here we evaluated the effects of a synthetic single-stranded cDNA (APT20TTMG) that interacts with U1 snRNP, in iPSC-derived neurons from a donor diagnosed with AD and in the SAMP8 mouse model. APT20TTMG effectively binds to U1 snRNP, specifically decreasing TAU in AD neurons, without changing mitochondrial activity or glutamate. Treatment enhanced neuronal electrical activity, promoted an enrichment of differentially expressed genes related to key processes affected by AD. In SAMP8 mice, APT20TTMG reduced insoluble pTAU in the hippocampus, amyloid-beta and GFAP in the cortex, and U1-70 K in both brain regions, without cognitive changes. This study highlights the correction of the U1 snRNP complex as a new target for AD.Lire moins >

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Date de dépôt :

2024-12-17T22:00:51Z
2025-02-19T12:35:46Z