Echinometra lucunter molecules reduce Aß42-induced neurotoxicity in SH-SY5Y neuron-like cells: effects on disaggregation and oxidative stress.

Background: Echinometra lucunter is a sea urchin commonly found on America's rocky shores. Its coelomic fluid contains molecules used for defense and biological processes, which may have therapeutic potential for the treatment of amyloid-based neurodegenerative diseases, such as Alzheimer's, that currently have few drug options available. Methods: In this study, we incubated E. lucunter coelomic fluid (ELCF) and fractions obtained by solid phase extraction in SH-SY5Y neuron-like cells to evaluate their effect on cell viability caused by the oligomerized amyloid peptide 42 (Aß42o). Moreover, the Aß42o was quantified after the incubation with ELCF fractions in the presence or not of cells, to evaluate if samples could cause amyloid peptide disaggregation. Antioxidant activity was determined in ELCF fractions, and cells were evaluated to check the oxidative stress after incubation with samples. The most relevant fraction was analyzed by mass spectrometry for identification of molecules. Results: ELCF and certain fractions could prevent and treat the reduction of cell viability caused by Aß42o in SH-SY5Y neuron-like cells. We found that one fraction (El50) reduced the oligomerized Aß42 and the oxidative stress caused by the amyloid peptide through its antioxidant molecules, which in turn reduced cell death. Mass spectrometry analysis revealed that El50 comprises small molecules containing flavonoid antioxidants, such as phenylpyridazine and dihydroquercetin, and two peptides. Conclusion: Our results suggest that sea urchin molecules may interact with Aß42o and oxidative stress, preventing or treating neurotoxicity, which may be useful in treating dementia.

Aquaporin-4 Mediated Aggregation of Alzheimer's Amyloid ß-Peptide.

Clearance of Alzheimer's amyloid oligomers from the brain is crucial for preventing cell toxicity. Dementia complications arise as a result of apoptosis, which is caused by peptide plaques on the lipid surface of cells. Here, we employed all-atom and coarse-grained molecular dynamics simulations to investigate the aggregation of amyloid peptides at the lipid surface and the role of aquaporin-4 (AQP4) in facilitating peptide clearance from astrocytes. The network of protein-protein interactions through text mining revealed that the expression of AQP4 and amyloid aggregation were strongly correlated. It has also been revealed that the role of aquaporins in the etiology of Alzheimer's disease involves several interconnected proteins and pathways. The nature of aggregation at the surface of the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer was revealed by the interaction of amyloid oligomers. The membrane-bound pore region of AQP4 interacts with the peptide and slows its aggregation. This interaction maintains the helical content of the peptide while lowering its toxicity at the lipid surface. The hydrophobicity of the peptide also decreased because of these interactions, which may help in the removal of the peptide from astrocytes. Long-term coarse-grained MD simulations demonstrated different features of oligomer aggregation at the surface and strong oligomer attraction to AQP4, which inhibited aggregation. Additionally, the water dynamics of aquaporins demonstrate how the selectivity filter is broken to disrupt water flow. Our findings also provide insight into the physiological alterations in brain tissue associated with Alzheimer's disease, including water retention and increased water flow in the CSF. Furthermore, in vitro thioflavin fluorescence spectroscopy revealed a slower aggregation of the peptide in the presence of AQP4.

Echinometra lucunter molecules reduce Aβ42-induced neurotoxicity in SH-SY5Y neuron-like cells: effects on disaggregation and oxidative stress

Echinometra lucunter is a sea urchin commonly found on America’s rocky shores. Its coelomic fluid contains molecules used for defense and biological processes, which may have therapeutic potential for the treatment of amyloid-based neurodegenerative diseases, such as Alzheimer’s, that currently have few drug options available. Methods: In this study, we incubated E. lucunter coelomic fluid (ELCF) and fractions obtained by solid phase extraction in SH-SY5Y neuron-like cells to evaluate their effect on cell viability caused by the oligomerized amyloid peptide 42 (Aβ42o). Moreover, the Aβ42o was quantified after the incubation with ELCF fractions in the presence or not of cells, to evaluate if samples could cause amyloid peptide disaggregation. Antioxidant activity was determined in ELCF fractions, and cells were evaluated to check the oxidative stress after incubation with samples. The most relevant fraction was analyzed by mass spectrometry for identification of molecules. Results: ELCF and certain fractions could prevent and treat the reduction of cell viability caused by Aβ42o in SH-SY5Y neuron-like cells. We found that one fraction (El50) reduced the oligomerized Aβ42 and the oxidative stress caused by the amyloid peptide through its antioxidant molecules, which in turn reduced cell death. Mass spectrometry analysis revealed that El50 comprises small molecules containing flavonoid antioxidants, such as phenylpyridazine and dihydroquercetin, and two peptides. Conclusion: Our results suggest that sea urchin molecules may interact with Aβ42o and oxidative stress, preventing or treating neurotoxicity, which may be useful in treating dementia.

Association of β-amyloid peptide 40/42 with type 2 diabetes mellitus and atherosclerosis / 中华内分泌代谢杂志

Serum p-amyloid peptide(Aβ)40 and Ap42 levels in patients with type 2 diabetes mellitus (T2DM)and atherosclerosis(AS)were detected by ELISA.The results showed that serum Ap40 level in T2DM group was significantly higher than that in the control group[(274.70±159.51 vs 162.63±87.58)pg/ml,P<0.05],especially in the diabetic patients accompanied with AS[(616.95±195.13)pg/m],P<0.01].Serum Ap40 level in simple AS group was also higher than that in control group[(318.52± 188.65)pg/ml,P<0.05].These results suggest that Ap40 is a risk factor of T2DM complicated with AS.However,there was no difference in serum Ap42 levels among various groups.