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Título
Calreticulin (crt-1) silencing reduces Aß1–42-induced toxicity and restores muscle function in C. elegans.
Autor
Año del Documento
2025
Editorial
Elsevier
Descripción
Producción Científica
Documento Fuente
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2025, vol. 1871, n. 7, p. 167946
Resumen
Accumulation of aggregated β-amyloid peptide is a key histopathological feature of Alzheimer's Disease (AD). Experimental models of AD based on β-amyloid peptide display calcium (Ca2+) signaling alterations, and targeting key components of the cellular Ca2+ signaling system has been postulated to modulate AD onset and progression. Here we have taken advantage of a C. elegans strain that over-expresses the most toxic human ß-amyloid peptide (Aß1–42) in body-wall muscle cells, to study the impact of calreticulin (crt-1) silencing on body-wall muscle performance. Crt-1 knockdown reduced the percentage of paralyzed worms in a dose-dependent manner and improved locomotion parameters in free-mobility assays in Aß1–42-overexpressing worms. At the cellular level, crt-1 silencing prevented Aß1–42-induced exacerbated mitochondrial respiration and mitochondrial ROS production without impacting mitochondrial sarcomere organization. Crt-1 knockdown reduced the number and size of Aß1–42 aggregates in body-wall muscle cells and prevented the formation of Aß1–42 oligomers. We propose that crt-1 depletion reduces the number of Aß1–42 aggregates, precluding Aß1–42-induced mitochondrial toxicity and improving muscle function. We identify C. elegans crt-1 as a gene involved in the toxicity associated with the expression of human Aß1–42, and thus a potential new target for treatment.
Materias Unesco
2302 Bioquímica
Palabras Clave
C. elegans
Calreticulin
Crt-1
Alzheimer's disease
Beta-amyloid
Mitochondria
Ca2+ signaling
ISSN
0925-4439
Revisión por pares
SI
Patrocinador
Ministerio de Ciencia e Innovación de España [Ref. PID2021-122239OB-I00, cofinanciada por la Unión Europea a través del Fondo Europeo de Desarrollo Regional]
Junta de Castilla y León [Ref. CL-EI-2021]
Universidad de Valladolid [POSTDOC SEN-2019 UVA27]
Junta de Castilla y León [Ref. CL-EI-2021]
Universidad de Valladolid [POSTDOC SEN-2019 UVA27]
Version del Editor
Propietario de los Derechos
© 2025 The Author(s)
Idioma
eng
Tipo de versión
info:eu-repo/semantics/publishedVersion
Derechos
openAccess
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