The unfolded protein response in amyotrophic later sclerosis: Results of a phase 2 trial
نویسندگان
چکیده
Robust preclinical findings demonstrated that guanabenz selectively inhibits ER stress-induced eIF2α-phosphatase allowing misfolded protein clearance, reduces neuronal death and prolongs survival in vitro vivo ALS models.
منابع مشابه
The unfolded protein response in familial amyotrophic lateral sclerosis.
Mutant superoxide dismutase type 1 (MTSOD1) is thought to cause ∼20% of cases of familial amyotrophic lateral sclerosis (FALS) because it misfolds and aggregates. Previous studies have shown that MTSOD1 accumulates inside the endoplasmic reticulum (ER) and activates the unfolded protein response (UPR), suggesting that ER stress is involved in the pathogenesis of FALS. We used a genetic approach...
متن کاملThe unfolded protein response in multiple sclerosis
The unfolded protein response (UPR) occurs in response to endoplasmic reticulum (ER) stress caused by the accumulation of unfolded or misfolded proteins in the ER. The UPR is comprised of three signaling pathways that promote cytoprotective functions to correct ER stress; however, if ER stress cannot be resolved the UPR results in apoptosis of affected cells. The UPR is an important feature of ...
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OBJECTIVES Ceftriaxone increases expression of the astrocytic glutamate transporter, EAAT2, which might protect from glutamate-mediated excitotoxicity. A trial using a novel three stage nonstop design, incorporating Phases I-III, tested ceftriaxone in ALS. Stage 1 determined the cerebrospinal fluid pharmacokinetics of ceftriaxone in subjects with ALS. Stage 2 evaluated safety and tolerability f...
متن کاملRole of Oxidative Stress in Modulating Unfolded Protein Response Activity in Chronic Myeloid Leukemia Cell Line
Background: Recently, it has been revealed that tyrosine kinase inhibitors (TKIs) act through inducing both oxidative and endoplasmic reticulum (ER) stress in chronic myeloid leukemia cells. However, ER stress signaling triggers both apoptotic and survival processes within cells. Nevertheless, mechanisms by which TKIs avoid the pro-survival effects are not clear. The aim of this study was to ev...
متن کاملThe unfolded protein response
Where does the UPR function? Between the endoplasmic reticulum (ER) and the nucleus of eukaryotic cells. All secreted proteins and proteins that reside in secretory compartments translocate as nascent peptide chains into the ER, where they may undergo folding, modification and assembly before assuming their functional conformations. The ER maintains a specialized oxidizing environment to aid ch...
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ژورنال
عنوان ژورنال: Journal of the Neurological Sciences
سال: 2021
ISSN: ['0022-510X', '1878-5883']
DOI: https://doi.org/10.1016/j.jns.2021.117702