Articles: amyloid-metabolism.
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Alzheimer's disease is one of the most common causes of dementia. It is believed that the aggregation of short Aβ-peptides to form oligomeric and protofibrillar amyloid assemblies plays a central role for disease-relevant neurotoxicity. In recent years, passive immunotherapy has been introduced as a potential treatment strategy with anti-amyloid antibodies binding to Aβ-amyloids and inducing their subsequent degradation by the immune system. ⋯ Indeed, an aggregate-specific N-terminal binding motif was found in case of Aducanumab binding to oligomers, protofilaments and fibrils that is located next to but not overlapping with the epitope binding site found in the crystal structure with Aβ2 - 7. Analysis of binding energetics indicates that this motif binds weaker than the epitope but likely contributes to Aducanumab's preference for aggregated Aβ-species. The predicted aggregate-specific binding motif could potentially serve as a basis to reengineer Aducanumab for further enhanced preference to bind Aβ-aggregates vs monomers.
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Alzheimer's disease (AD) is one the most common types of dementia. Plaques of amyloid beta and neurofibrillary tangles of tau are two major hallmarks of AD. Metabolism of these two proteins, in part, depends on autophagy pathways. Autophagy dysfunction and protein aggregation in AD may be involved in a vicious circle. The aim of this study was to investigate whether tau or amyloid beta 42 (Aβ42) could affect expression of autophagy genes, and whether they exert their effects in the same way or not. ⋯ We conclude that both Aβ42 and Tau R406W may affect autophagy through dysregulation of autophagy genes. Interestingly, it seems that these pathological proteins exert their toxic effects on autophagy through different pathways and independently.
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As more older adults undergo surgery, it is critical to understand the long-term effects of surgery on brain health, particularly in relation to the development of Alzheimer's disease. This study examined the association of surgical hospitalization with subsequent brain β-amyloid deposition in nondemented older adults. ⋯ The results do not support an association between surgical hospitalization and elevated brain amyloid.
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Deterioration of energy metabolism in affected cells is an important feature of synucleinopathies, including Parkinson's disease. Here, we studied the association between α-synuclein accumulation and glycolysis using SH-SY5Y neuroblastoma cell lines stably expressing wild-type α-synuclein or its A53T mutant linked to the autosomal dominant form of the disease. Overexpression of both proteins led to the accumulation of thioflavin S-positive aggregates, more pronounced for α-synuclein A53T. ⋯ Impairments in glycolysis were also accompanied by a decrease in the activity of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In vitro experiments with purified proteins indicated that GAPDH inactivation might be caused by its binding to the monomeric and oligomeric forms of α-synuclein. Therefore, a decrease in the GAPDH activity induced by its interaction with α-synuclein, might be one of the causes of glucose metabolism deterioration in synucleinopathies.