Publications by authors named "Stefanos Aivazidis"

mutations that encode lysosomal β-glucocerebrosidase (GCase) cause the lysosomal storage disorder Gaucher disease (GD) and are strong risk factors for synucleinopathies, including Parkinson's disease and Lewy body dementia. Only a subset of subjects with mutations exhibit neurodegeneration, and the factors that influence neurological phenotypes are unknown. We find that α-synuclein (α-syn) neuropathology induced by GCase depletion depends on neuronal maturity, the physiological state of α-syn, and specific accumulation of long-chain glycosphingolipid (GSL) GCase substrates.

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Mitochondrial superoxide (O) production is implicated in aging, neurodegenerative disease, and most recently epilepsy. Yet the specific contribution of neuronal O to these phenomena is unclear. Here, we selectively deleted superoxide dismutase-2 (SOD2) in neuronal basic helix-loop-helix transcription factor (NEX)-expressing cells restricting deletion to a subset of excitatory principle neurons primarily in the forebrain (cortex and hippocampus).

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Down syndrome (DS) is a chromosomal disorder caused by trisomy of chromosome 21 (Ts21). Unbalanced karyotypes can lead to dysfunction of the proteostasis network (PN) and disrupted proteostasis is mechanistically associated with multiple DS comorbidities. Autophagy is a critical component of the PN that has not previously been investigated in DS.

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Disruption in redox signaling and control of cellular processes has emerged as a key player in many pathologies including neurodegeneration. As protein aggregations are a common hallmark of several neuronal pathologies, a firm understanding of the interplay between redox signaling, oxidative and free radical stress, and proteinopathies is required to sort out the complex mechanisms in these diseases. Fortunately, models of toxicant-induced neurodegeneration can be utilized to evaluate and report mechanistic alterations in the proteostasis network (PN).

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Article Synopsis
  • - The study investigates how cholestatic liver diseases like primary sclerosing cholangitis (PSC) contribute to oxidative stress and inflammation, using liver tissue samples from different mouse models and human patients.
  • - Findings show that Mdr2 mice had significant liver fibrosis and increased reactive aldehydes, with specific proteins related to antioxidant defenses showing elevated expression in response to cholestatic injury.
  • - Mass spectrometric analysis identified more carbonylated proteins in Mdr2 and PSC groups, indicating that cholestasis leads to heightened oxidative stress through changes in metabolic and signaling processes, especially concerning protein carbonylation.
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The pesticides paraquat (PQ) and maneb (MB) have been described as environmental risk factors for Parkinson's disease (PD), with mechanisms associated with mitochondrial dysfunction and reactive oxygen species generation. A combined exposure of PQ and MB in murine models and neuroblastoma cells has been utilized to further advance understanding of the PD phenotype. MB acts as a redox modulator through alkylation of protein thiols and has been previously characterized to inhibit complex III of the electron transport chain and uncouple the mitochondrial proton gradient.

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Article Synopsis
  • Cystathionine β-synthase-deficient homocystinuria (HCU) disrupts sulfur metabolism, leading to reduced levels of important molecules like cysteine and glutathione in liver cells.
  • A mouse model of HCU shows increased expression of enzymes involved in glutathione synthesis and detoxification processes, despite no activation of the Nrf2 antioxidant response pathway.
  • Taurine treatment effectively normalizes levels of key enzymes and mitigates the negative effects on glutathione, highlighting its potential as a therapeutic option for HCU and related conditions involving glutathione depletion.
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Down syndrome (DS) is a genetic disorder caused by trisomy of chromosome 21. Abnormalities in chromosome number have the potential to lead to disruption of the proteostasis network (PN) and accumulation of misfolded proteins. DS individuals suffer from several comorbidities, and we hypothesized that disruption of proteostasis could contribute to the observed pathology and decreased cell viability in DS.

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In the present study, the in vitro scavenging activity of sheep whey protein against free radicals, as well as its reducing power were determined and compared with that of beef protein, soy protein and cow whey protein. Moreover, the possible protective effects of sheep whey protein from tert-butyl hydroperoxide (tBHP)-induced oxidative stress in muscle C2C12 cells were determined by assessing oxidative stress markers by flow cytometry and spectrophotometry. The results showed that sheep whey protein scavenged DPPH, ABTS(+) and OH radicals with IC50 values of 3.

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