Publications by authors named "Jose E Marin"
Amyloid beta (Aβ) aggregation is generally associated with Alzheimer's onset. Here, we demonstrate that incubation of dopaminergic SH-SY5Y cells with an Aβ peptide fragment (an 11-mer composed of residues 25-35; Aβ (25-35)) results in elevated intracellular nitrosative stress and induces chemical mutation of protein disulfide isomerase (PDI), an endoplasmic reticulum-resident oxidoreductase chaperone. Furthermore, Aβ (25-35) provokes aggregation of both the minor and major biomarkers of Parkinson's disease, namely, synphilin-1 and α-synuclein, respectively.
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- Endoplasmic reticulum (ER) proteins, specifically protein disulfide isomerase (PDI), are essential for proper protein folding, but under nitrosative stress, PDI loses functionality due to S-nitrosylation, leading to protein aggregation, particularly α-synuclein.
- Ferrostatin-1 (Fer-1) is a small molecule antioxidant that prevents ferroptosis, a type of non-apoptotic cell death caused by oxidative stress, and has been shown to be non-toxic to dopaminergic neuroblastoma cells up to certain concentrations.
- In experiments, Fer-1 significantly reduces reactive oxygen and nitrogen species (ROS/RNS)
Nitrosative stress mediated S-nitrosylation (SNO) of protein disulfide isomerase (PDI), a housekeeping oxidoreductase, has been implicated in the pathogenesis of sporadic Parkinson's (PD) and Alzheimer's (AD) diseases. Previous cell line studies have indicated that SNO-PDI formation provokes synphilin-1 aggregation, the minor Parkinsonian biomarker protein. Yet no work exists investigating whether SNO-PDI induces α-synuclein aggregation, the major Lewy body constituent associated with Parkinson's pathogenesis.
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