Sigma-1 receptor agonist PRE084 is protective against mutant huntingtin-induced cell degeneration: involvement of calpastatin and the NF-kappa B pathway

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Hyrskyluoto A, Pulli I, Törnqvist K, Ho TH, Korhonen L, Lindholm D
Förläggare: NATURE PUBLISHING GROUP
Publiceringsår: 2013
Tidskrift: Cell Death and Disease
Tidskriftsakronym: CELL DEATH DIS
Volym: 4
Antal sidor: 9
ISSN: 2041-4889


Abstrakt

Alterations in mitochondria and increased oxidative stress are associated with the disease progression in Huntington's disease (HD). Endoplasmic reticulum (ER) stress and oxidative damage are linked through the close communication between the ER and mitochondria. Sigma-1 receptor (Sig-1R) is a chaperone protein in the ER that is involved in ER stress regulation, but little is known about its role in HD or the mechanisms for cell protection. Here we show that the Sig-1R agonist, PRE084 increases cell survival and counteracts the deleterious effects caused by N-terminal mutant huntingtin proteins in neuronal PC6.3 cells. Particularly, PRE084 increased the levels of cellular antioxidants by activating the NF-kappa B pathway that is compromised by the expression of mutant huntingtin proteins. These results show that the Sig-1R agonist has beneficial effects in models of HD and that compounds affecting the Sig-1R may be promising targets for future drug development in HD.


Nyckelord

calpastatin, HD, NF-kappa B, Sigma-1 receptor

Senast uppdaterad 2020-23-01 vid 04:32