Main text The disruption of protein folding homeostasis in motoneurons(MNs)and the accumulation of protein aggregates are some of the main molecular hallmarks of amyotrophic lateral sclerosis(ALS).Evidence from sporad...Main text The disruption of protein folding homeostasis in motoneurons(MNs)and the accumulation of protein aggregates are some of the main molecular hallmarks of amyotrophic lateral sclerosis(ALS).Evidence from sporadic and familial ALS(fALS)patients and from ALS models suggests that protein aggregation directly participates in neurodegeneration.In turn,the loss of MN homeostasis triggers a coping mechanism,the integrated stress response(ISR)[1].The ISR is initiated by four independent stress-sensing kinases,each of them activated by distinct stresses:protein kinase R(PKR)by double-strand RNA,protein kinase RNA-like endoplasmic reticulum kinase(PERK)by protein misfolding at the endoplasmic reticulum(ER),general control nonderepressible 2(GCN2)by nutrient starvation,and heme-regulated inhibitor(HRI)by heme deprivation.展开更多
基金supported by PID2020-120497RB-I00 MCIU/AEI/https://doi.org/10.13039/501100011033,BFU2017-90043-P MCINN/AEI/https://doi.org/10.13039/501100011033/by FEDER“Una manera de hacer Europa”(MA and TA),Proyecto Intramural IdisNa 2022(MA),Fundación para la Investigación Médica Aplicada(FIMA)Proyectos I+D,2017(TA)and Fundación Occident and DalecandELA Association(MA)supported by República de Panamá,Programa de Becas IFARHU-SENACYT(reference number 270-2018-922),NP by AC FIMA pre-doctoral fellowship.
文摘Main text The disruption of protein folding homeostasis in motoneurons(MNs)and the accumulation of protein aggregates are some of the main molecular hallmarks of amyotrophic lateral sclerosis(ALS).Evidence from sporadic and familial ALS(fALS)patients and from ALS models suggests that protein aggregation directly participates in neurodegeneration.In turn,the loss of MN homeostasis triggers a coping mechanism,the integrated stress response(ISR)[1].The ISR is initiated by four independent stress-sensing kinases,each of them activated by distinct stresses:protein kinase R(PKR)by double-strand RNA,protein kinase RNA-like endoplasmic reticulum kinase(PERK)by protein misfolding at the endoplasmic reticulum(ER),general control nonderepressible 2(GCN2)by nutrient starvation,and heme-regulated inhibitor(HRI)by heme deprivation.
