Publications by authors named "Shamchal Bakavayev"
Article Synopsis
- A new antibody, scFv-SE21, specifically targets a part of misfolded SOD1 that is linked to its harmful behavior, without affecting healthy proteins.
- In studies using mice, delivering scFv-SE21 via a virus improved neuron health, reduced misfolded SOD1 levels, decreased neuroinflammation, and significantly increased survival rates, highlighting a potential new treatment strategy for ALS.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurons. About 20% of familial ALS cases are caused by dominant mutations in SOD1. It has been suggested that toxicity of mutant SOD1 results from its misfolding, however, it is unclear why misfolded SOD1 accumulates within specific tissues.
View Article and Find Full Text PDFUpon losing its structural integrity (misfolding), SOD1 acquires neurotoxic properties to become a pathogenic protein in ALS, a neurodegenerative disease targeting motor neurons; understanding the mechanism of misfolding may enable new treatment strategies for ALS. Here, we reported a monoclonal antibody, SE21, targeting the β6/β7-loop region of SOD1. The exposure of this region is coupled to metal loss and is entirely reversible during the early stages of misfolding.
View Article and Find Full Text PDFDespite different phenotypic manifestations, mounting evidence points to similarities in the molecular basis of major neurodegenerative diseases (ND). CNS has evolved to be robust against hazard of ROS, a common perturbation aerobic organisms are confronted with. The trade-off of robustness is system's fragility against rare and unexpected perturbations.
View Article and Find Full Text PDFThe Cu/Zn-superoxide dismutase (SOD1) is a ubiquitous enzyme that catalyzes the dismutation of superoxide radicals to oxygen and hydrogen peroxide. In addition to this principal reaction, the enzyme is known to catalyze, with various efficiencies, several redox side-reactions using alternative substrates, including biological thiols, all involving the catalytic copper in the enzyme's active-site, which is relatively surface exposed. The accessibility and reactivity of the catalytic copper is known to increase upon SOD1 misfolding, structural alterations caused by a mutation or environmental stresses.
View Article and Find Full Text PDFArticle Synopsis
- * The study reveals that BIM-BH3, a protein involved in cell death, interacts with the Aβ42 peptide, affecting its structure and behavior, including inhibiting its fibril formation while promoting other types of aggregates.
- * The interaction between BIM-BH3 and Aβ42 was found to induce cell death in a neuroblastoma cell model, suggesting a crucial connection between these components and neuronal cell death in Alzheimer's disease.