In situ fibrillizing amyloid-beta 1-42 induces neurite degeneration and apoptosis of differentiated SH-SY5Y cells

Abstract

The progression of Alzheimer’s disease is causatively linked to the accumulation of amyloid-β aggregates in the brain, however, it is not clear how the amyloid aggregates initiate the death of neuronal cells. The in vitro toxic effects of amyloid peptides are most commonly examined using the human neuroblastoma derived SH-SY5Y cell line and here we show that differentiated neuron-like SH-SY5Y cells are more sensitive to amyloid peptides than non-differentiated cells, because the latter lack long neurites. Exogenous soluble amyloid-β 1–42 covered cell bodies and whole neurites in differentiated cells with dense fibrils, causing neurite beading and fragmentation, whereas preformed amyloid-β 1–42 fibrils had no toxic effects. Importantly, spontaneously fibrillizing amyloid-β 1–42 peptide exhibited substantially higher cellular toxicity than amyloid-β 1–40, which did not form fibrils under the experimental conditions. These results support the hypothesis that peptide toxicity is related to the active fibrillization process in the incubation mixture.

Xenobiotic compounds modulate cytotoxicity of Aβ amyloids and interact with neuroprotective chaperone L-PGDS

“…6C).The MTT metabolic assay was employed to investigate the cytotoxicity of the Aβ(1-40) fibrils grown in the presence of the xenobiotic compounds -9,10 PQ, CPM and TRD in SH-SY5Y cells. The Aβ(1-40) fibril control did not exhibit any significant effect on the viability of the SH-SY5Y cells as also shown previously by Krishtal et al[37]. In contrast, exposure to Aβ(1-40) fibrils grown in the presence of CPM in a molar ratio of 1:1, resulted in a significant decrease in the viability of SH-SY5Y cells, a 66.19% of the control.…”

Exploring the Multi-Target Performance of Mitochondriotropic Antioxidants against the Pivotal Alzheimer’s Disease Pathophysiological Hallmarks

“…In this work, the neuroprotective potential of the mitochondriotropic antioxidants under study was evaluated toward aggressors (glutamate, iron(III) and Aβ 42 ) related with excitotoxicity, iron accumulation and protein misfolding and aggregation, which are deeply related to AD progression and neuronal death [25,40,41]. The cytotoxic profile at the same concentrations has been reported [32].…”

High molecular weight amyloid β 1‐42 oligomers induce neurotoxicity via plasma membrane damage

“…The cells were cultured in DMEM and Ham's F-12 medium that contained 10% fetal bovine serum and antibiotic-antimycotic solution, and they were maintained under a humidified atmosphere of 5% CO 2 and 95% air at 37°C. SH-SY5Y cells are similar to neurons in terms of their morphologic and neurochemical properties, and they have been widely used to evaluate neuronal injury and death in response to neurotoxins and cerebral ischemia-reperfusion as in vitro disease models (28). To evaluate the effects of Ab 1-42 , SH-SY5Y cells were initially differentiated with all-trans retinoic acid.…”