Effects of Amyloid-β Peptide on the Biology of Human Neural Stem Cells

Bernabeu-Zornoza, Adela; Coronel, Raquel; Lachgar, María; Palmer, Charlotte; Liste, Isabel

doi:10.1007/978-1-4939-7816-8_23

Cited by 4 publications

(4 citation statements)

References 15 publications

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“…As mature HEWL and Aβ(1–40) fibrillar aggregates are not toxic, it is conceivable that surface-directed Aβ(1–40) and HEWL fibrils were the toxic amyloid structures, and the presence of the negatively charged surface in vivo may help convert the non-toxic amyloidogenic aggregates into toxic amyloidogenic structures. Previous studies reveal that formation of amyloidogenic species can directly affect NSCs during the development of neurodegenerative diseases . Evidence suggests that Aβ amyloids lead to NSC death and differentiation, which may exhaust the stem cell pool and hinder the healing process of the neural system.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies reveal that formation of amyloidogenic species can directly affect NSCs during the development of neurodegenerative diseases. 79 Evidence suggests that Aβ amyloids lead to NSC death and differentiation, 80 which may exhaust the stem cell pool and hinder the healing process of the neural system. In this study, NSC differentiation and self-maintenance are assessed at the single cell level by tracking Hes5-GFP expression (indicative of self-renewing NSCs) and Dcx-RFP to label neuroblasts (indicating progress towards differentiation).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Surface-Directed Structural Transition of Amyloidogenic Aggregates and the Resulting Neurotoxicity

et al. 2020

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The transition of amyloidogenic species into ordered structures (i.e., prefibrillar oligomers, protofibrils, mature fibrils, and amyloidogenic aggregates) is closely associated with many neurodegenerative disease pathologies. It is increasingly appreciated that the liquid−solid interface contributes to peptide aggregation under physiological conditions. However, much remains to be explored on the molecular mechanism of surface-directed amyloid formation. We herein demonstrate that physical environmental conditions (i.e., negatively charged surface) affect amyloid formation. Nontoxic amyloid aggregates quickly develop into intertwisting fibrils on a negatively charged mica surface. These fibrillar structures show significant cytotoxicity on both neuroblastoma cell-lines (SH-SY5Y) and primary neural stem cells. Our results suggest an alternative amyloid development pathway, following which Aβ peptides form large amyloidogenic aggregates upon stimulation, and later transit into neurotoxic fibrillar structures while being trapped and aligned by a negatively charged surface. Conceivably, the interplay between chemical and physical environmental conditions plays important roles in the development of neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Surface-Directed Structural Transition of Amyloidogenic Aggregates and the Resulting Neurotoxicity

et al. 2020

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“…Fibrillary Aβ42 peptides were prepared by diluting the dry stock in DMSO to 5 mM, then further diluting to 100 µM in 10 mM hydrochloric acid solution (prepared in ultrapure H2O from a 1 M HCl stock; Merk; 1.00317.1000), and the aliquot was left at 37 • C for 24 h. The next day, the aliquot was diluted to different concentrations for analysis (0.5, 1, and 5 µM) in cell differentiation medium immediately before it adding to cells. hNS1 cells were treated for the first 4.5 days of differentiation [46]. Untreated cells and vehicle (DMSO)-treated cells were used as controls.…”

Section: Preparation and Treatment With Aβ Peptidementioning

confidence: 99%

Oligomeric and Fibrillar Species of Aβ42 Diversely Affect Human Neural Stem Cells

Bernabeu-Zornoza

Coronel

Palmer

et al. 2021

IJMS

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Amyloid-β 42 peptide (Aβ1-42 (Aβ42)) is well-known for its involvement in the development of Alzheimer’s disease (AD). Aβ42 accumulates and aggregates in fibers that precipitate in the form of plaques in the brain causing toxicity; however, like other forms of Aβ peptide, the role of these peptides remains unclear. Here we analyze and compare the effects of oligomeric and fibrillary Aβ42 peptide on the biology (cell death, proliferative rate, and cell fate specification) of differentiating human neural stem cells (hNS1 cell line). By using the hNS1 cells we found that, at high concentrations, oligomeric and fibrillary Aβ42 peptides provoke apoptotic cellular death and damage of DNA in these cells, but Aβ42 fibrils have the strongest effect. The data also show that both oligomeric and fibrillar Aβ42 peptides decrease cellular proliferation but Aβ42 oligomers have the greatest effect. Finally, both, oligomers and fibrils favor gliogenesis and neurogenesis in hNS1 cells, although, in this case, the effect is more prominent in oligomers. All together the findings of this study may contribute to a better understanding of the molecular mechanisms involved in the pathology of AD and to the development of human neural stem cell-based therapies for AD treatment.

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“…This study brought a new perspective to rethink the molecular targets relevant for endogenous NSC-based strategies in AD. The effects of A β peptides on NSCs are still not well understood and remain controversial, and the necessity for their study has been outlined recently [6]. The second major pathological hallmark of AD is an accumulation of hyperphosphorylated tau protein, induced upon oxidative stress signalling.…”

Section: Introductionmentioning

confidence: 99%

Oxidative DNA Damage Signalling in Neural Stem Cells in Alzheimer’s Disease

Kieroń

Żekanowski

Falk

et al. 2019

Oxidative Medicine and Cellular Longevity

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The main pathological symptoms of Alzheimer's disease (AD) are β-amyloid (Aβ) lesions and intracellular neurofibrillary tangles of hyperphosphorylated tau protein. Unfortunately, existing symptomatic therapies targeting Aβ and tau remain ineffective. In addition to these pathogenic factors, oxidative DNA damage is one of the major threats to newborn neurons. It is necessary to consider in detail what causes neurons to be extremely susceptible to oxidative damage, especially in the early stages of development. Accordingly, the regulation of redox status is crucial for the functioning of neural stem cells (NSCs). The redox-dependent balance, of NSC proliferation and differentiation and thus the neurogenesis process, is controlled by a series of signalling pathways. One of the most important signalling pathways activated after oxidative stress is the DNA damage response (DDR). Unfortunately, our understanding of adult neurogenesis in AD is still limited due to the research material used (animal models or post-mortem tissue), providing inconsistent data. Now, thanks to the advances in cellular reprogramming providing patient NSCs, it is possible to fill this gap, which becomes urgent in the light of the potential of their therapeutic use. Therefore, a decent review of redox signalling in NSCs under physiological and pathological conditions is required. At this moment, we attempt to integrate knowledge on the influence of oxidative stress and DDR signalling in NSCs on adult neurogenesis in Alzheimer's disease.

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Effects of Amyloid-β Peptide on the Biology of Human Neural Stem Cells

Cited by 4 publications

References 15 publications

Surface-Directed Structural Transition of Amyloidogenic Aggregates and the Resulting Neurotoxicity

Surface-Directed Structural Transition of Amyloidogenic Aggregates and the Resulting Neurotoxicity

Oligomeric and Fibrillar Species of Aβ42 Diversely Affect Human Neural Stem Cells

Oxidative DNA Damage Signalling in Neural Stem Cells in Alzheimer’s Disease

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