scholarly journals GM1 mediates the formation and maintenance of cytotoxic Aβ oligomers

2021 ◽  
Author(s):  
Dongyan Zhang ◽  
Jian Wang ◽  
Rebecca M Fleeman ◽  
Madison K Kuhn ◽  
Matthew T Swulius ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Amyloid Beta ◽  
Pharmaceutical Research ◽  
Neuronal Cell ◽  
Membrane Composition ◽  
Aβ Oligomers ◽  
Cell Viability Assay ◽  
Oligomer Formation ◽  
Viability Assay ◽  
Beta Peptide

The aggregation of amyloid beta peptide is associated with Alzheimer's disease (AD) pathogenesis. Cell membrane composition, especially monosialotetrahexosylganglioside (GM1), is known to promote the formation of amyloid beta; fibrils, yet little is known about the roles of GM1 in the early steps of amyloid beta; oligomer formation. Here, by using GM1-contained liposomes as a mimic of neuronal cell membrane, we demonstrate that GM1 is a critical trigger of amyloid beta; oligomerization and aggregation. We find that GM1 not only promotes the formation of amyloid beta; fibrils, but also facilitates the maintenance of amyloid beta; oligomers on liposome membranes. We structurally characterize the amyloid beta; oligomers formed on the membrane and find that GM1 captures amyloid beta; by binding to its arginine-5 residue. To interrogate the mechanism of amyloid beta; oligomer toxicity, we design a new liposome-based Ca2+-encapsulation assay and provide new evidence for the amyloid beta; ion channel hypothesis. Finally, we conduct cell viability assay to determine the toxicity of amyloid beta; oligomers formed on membranes. Overall, by uncovering the roles of GM1 in mediating early amyloid beta; oligomer formation and maintenance, our work provides a novel direction for pharmaceutical research for AD.

G-lymphatic, vascular and immune pathways for Aβ clearance cascade and therapeutic targets for Alzheimer’s disease

2020 ◽  
Vol 23 ◽  
Author(s):  
Saurav Chakraborty ◽  
Jyothsna ThimmaReddygari ◽  
Divakar Selvaraj
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Complement System ◽  
Therapeutic Targets ◽  
Neuronal Cell ◽  
Precursor Protein ◽  
Amyloid Beta Peptide ◽  
Beta Peptide ◽  
Immune Pathways

The Alzheimer disease is a age related neurodegenerative disease. The factors causing alzheimer disease are numerous. Research on humans and rodent models predicted various causative factors involved in Alzheimer disease progression. Among them, neuroinflammation, oxidative stress and apoptosis play a major role because of accumulation of extracellular amyloid beta peptides. Here, the clearance of amyloid beta peptide plays a major role because of the imbalance in the production and clearance of the amyloid beta peptide. Additionally, neuroinflammation by microglia, astrocytes, cytokines, chemokines and the complement system also have a major role in Alzheimer disease. The physiological clearance pathways involved in amyloid beta peptide are glymphatic, vascular and immune pathways. Amyloid precursor protein, low density lipoprotein receptor-related protein 1, receptor for advanced glycation end product, apolipoprotein E, clusterin, aquaporin 4, auto-antibodies, complement system, cytokines and microglia are involved in amyloid beta peptide clearance pathways across the blood brain barrier. The plaque formation in the brain by alternative splicing of amyloid precursor protein and production of misfolded protein results in amyloid beta agglomeration. This insoluble amyloid beta leads to neurodegenerative cascade and neuronal cell death occurs. Studies had shown disturbed sleep may be a risk factor for dementia and cognitive decline. In this review, the therapeutic targets for alzheimer disease via focussing on pathways for amyloid beta clearance are discussed.

scholarly journals BDMC protects AD in vitro via AMPK and SIRT1

2020 ◽  
Vol 11 (1) ◽  
pp. 319-327
Author(s):  
Chenlin Xu ◽  
Zijian Xiao ◽  
Heng Wu ◽  
Guijuan Zhou ◽  
Duanqun He ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Activity Measurement ◽  
Therapeutic Approaches ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Compound C

AbstractBackgroundAlzheimer’s disease (AD) is a common neurodegenerative disorder without any satisfactory therapeutic approaches. AD is mainly characterized by the deposition of β-amyloid protein (Aβ) and extensive neuronal cell death. Curcumin, with anti-oxidative stress (OS) and cell apoptosis properties, plays essential roles in AD. However, whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, can exert a neuroprotective effect in AD remains to be elucidated.MethodsIn this study, SK-N-SH cells were used to establish an in vitro model to investigate the effects of BDMC on the Aβ1–42-induced neurotoxicity. SK-N-SH cells were pretreated with BDMC and with or without compound C and EX527 for 30 min after co-incubation with rotenone for 24 h. Subsequently, western blotting, cell viability assay and SOD and GSH activity measurement were performed.ResultsBDMC increased the cell survival, anti-OS ability, AMPK phosphorylation levels and SIRT1 in SK-N-SH cells treated with Aβ1–42. However, after treatment with compound C, an AMPK inhibitor, and EX527, an SIRT1inhibitor, the neuroprotective roles of BDMC on SK-N-SH cells treated with Aβ1–42 were inhibited.ConclusionThese results suggest that BDMC exerts a neuroprotective role on SK-N-SH cells in vitro via AMPK/SIRT1 signaling, laying the foundation for the application of BDMC in the treatment of neurodegenerative diseases related to AMPK/SIRT1 signaling.

scholarly journals Quantitative analysis of co-oligomer formation by amyloid-beta peptide isoforms

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Marija Iljina ◽  
Gonzalo A. Garcia ◽  
Alexander J. Dear ◽  
Jennie Flint ◽  
Priyanka Narayan ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Amyloid Beta ◽  
Amyloid Beta Peptide ◽  
Oligomer Formation ◽  
Beta Peptide

scholarly journals Ubisol Coenzyme Q10 Promotes Mitochondrial Biogenesis in HT22 Cells Challenged by Glutamate

2019 ◽  
Author(s):  
Mary Zimmerman ◽  
Mia Hall ◽  
Qi Qi ◽  
Suresh L Mehta ◽  
Guisheng Chen ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Coenzyme Q10 ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ht22 Cells ◽  
Cell Viability Assay ◽  
Significant Deterioration ◽  
Significant Drop ◽  
Protein Levels ◽  
Viability Assay

Abstract Background: Glutamate-induced excitotoxicity is a well-recognized cause of neuronal cell death and nutritional supplementation with Coenzyme Q10 (CoQ10) has previously been shown to have neuro-protective actions against it. The objective of this study was to determine whether the protective effect of CoQ10 against glutamate could be attributed to stimulating mitochondrial biogenesis. Results: The mouse hippocampal neuronal HT22 cells were incubated with glutamate with or without ubisol Q10 treatment. Significant deterioration of cells after glutamate exposure was observed under a light microscope and cell viability assay, along with a significant drop in clonogenic ability. Glutamate significantly decreased the mitochondrial biogenesis related protein levels of Akt, CREB, PGC-1α, and NRF2, and reduced mitochondrial biogenesis assessed by a mitochondrial biogenesis kit. Pretreatment with CoQ10 prevented the decreases of Akt, CREB, PGC-1α, and NRF2 and increased mitochondrial biogenesis. Conclusions: Taken together, these results describe a new mechanism of CoQ10-conveyed neuro-protection and indicate a central role for mitochondrial biogenesis in protecting against glutamate-induced excitotoxicity.

scholarly journals 4,6′-Anhydrooxysporidinone from Fusarium lateritium SSF2 Induces Autophagic and Apoptosis Cell Death in MCF-7 Breast Cancer Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 869
Author(s):  
Dahae Lee ◽  
Sanghee Shim ◽  
Kisung Kang
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Neuronal Cell ◽  
Neuroprotective Effects ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Fusarium Lateritium ◽  
Caspase 7 ◽  
Mcf 7

Previous studies have reported that 4,6′-Anhydrooxysporidinone (SSF2-2), isolated from Fusarium lateritium SSF2, has neuroprotective effects on the HT-22 hippocampal neuronal cell line. However, the anti-cancer effect of SSF2-2 remains unclear. Here, we examined the viability of MCF-7 human breast cancer cells treated with SSF2-2 or left untreated using a cell viability assay kit. The underlying molecular mechanism was further investigated by Western blotting and immunocytochemistry studies. The results demonstrated that SSF2-2 inhibited the viability of MCF-7 cells. Treatment with SSF2-2 increased the levels of cleaved caspase-9, cleaved caspase-7, poly (ADP-ribose) polymerase (PARP), and LC3B. Additionally, SSF2-2 significantly increased the conversion of LC3-I to LC3II and LC3-positive puncta in MCF-7 cells.

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