RT info:eu-repo/semantics/article
T1 Calreticulin (crt-1) silencing reduces Aß1–42-induced toxicity and restores muscle function in C. elegans.
A1 Santo-Domingo, Jaime
A1 Caldero Escudero, Elena
A1 Romero Sanz, Silvia
A1 Alvarez-Illera, Pilar
A1 Fuente Pérez, Sergio De La
A1 García Casas, Paloma
A1 Fonteriz García, Rosalba Inés
A1 Montero, Mayte
A1 Álvarez Martín, Javier
K1 C. elegans
K1 Calreticulin
K1 Crt-1
K1 Alzheimer's disease
K1 Beta-amyloid
K1 Mitochondria
K1 Ca2+ signaling
K1 2302 Bioquímica
AB 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.
PB Elsevier
SN 0925-4439
YR 2025
FD 2025
LK https://uvadoc.uva.es/handle/10324/77016
UL https://uvadoc.uva.es/handle/10324/77016
LA eng
NO Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2025, vol. 1871, n. 7, p. 167946
NO Producción Científica
DS UVaDOC
RD 03-ago-2025