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Neurotoxicity Research

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01.10.2020 | Original Article

Genistein and Galantamine Combinations Decrease β-Amyloid Peptide _(1–42)–Induced Genotoxicity and Cell Death in SH-SY5Y Cell Line: an In Vitro and In Silico Approach for Mimic of Alzheimer’s Disease

verfasst von: Willian Orlando Castillo, Nilza Velasco Palomino, Catarina Satie Takahashi, Silvana Giuliatti

Erschienen in: Neurotoxicity Research | Ausgabe 3/2020

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Abstract

Alzheimer’s disease (AD) is the primary dementia-causing disease worldwide, involving a multifactorial combination of environmental, genetic, and epigenetic factors, with essential participation of age and sex. Biochemically, AD is characterized by the presence of abnormal deposition of beta amyloid peptide (Aβ_(1–42)), which in the brain is strongly correlated with oxidative stress, inflammation, DNA damage, and cholinergic impairment. The multiple mechanisms involved in its etiology create significant difficulty in producing an effective treatment. Neuroprotective properties of genistein and galantamine have been widely demonstrated through different mechanisms; however, it is unknown a possible synergistic neuroprotective effect against Aβ_(1–42). In order to understand how genistein and galantamine combinations regulate the mechanisms of neuroprotection, we conducted a set of bioassays in vitro to evaluate cell viability, clonogenic survival, cell death, and anti-genotoxicity. Through molecular docking and therapeutic viability assays, we analyzed the inhibitory activity exerted by genistein on three major protein targets (AChE, BChE, and NMDA) involved in AD. The results showed that genistein and galantamine afforded significant protection at higher concentrations; however, combinations of sub-effective concentrations of both compounds provided marked neuroprotection when they were combined. In silico approaches showed that genistein has higher scores than the positive controls and low toxicity levels; nevertheless, the therapeutic viability indicated that unlike galantamine, genistein cannot undergo the action by P glycoprotein (PGP) and probably may be unable to cross the blood-brain barrier. In conclusion, our results show that genistein and galantamine exert neuroprotective by decreasing genotoxicity and cell death. In silico analysis, suggest that genistein modulates positively the expression of AChE, BChE, and NMDA. In this context, a combination of two or more drugs could inspire an attractive therapeutic strategy.

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Titel: Genistein and Galantamine Combinations Decrease β-Amyloid Peptide (1–42)–Induced Genotoxicity and Cell Death in SH-SY5Y Cell Line: an In Vitro and In Silico Approach for Mimic of Alzheimer’s Disease
verfasst von: Willian Orlando Castillo
Nilza Velasco Palomino
Catarina Satie Takahashi
Silvana Giuliatti
Publikationsdatum: 01.10.2020
Verlag: Springer US
Erschienen in: Neurotoxicity Research / Ausgabe 3/2020
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-020-00243-8

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Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

29.05.2024 Hyponatriämie Nachrichten

Eine ältere Frau trinkt regelmäßig Sennesblättertee gegen ihre Verstopfung. Der scheint plötzlich gut zu wirken. Auf Durchfall und Erbrechen folgt allerdings eine Hyponatriämie. Nach deren Korrektur kommt es plötzlich zu progredienten Kognitions- und Verhaltensstörungen.

Schutz der Synapsen bei Alzheimer

29.05.2024 Morbus Alzheimer Nachrichten

Mit einem Neurotrophin-Rezeptor-Modulator lässt sich möglicherweise eine bestehende Alzheimerdemenz etwas abschwächen: Erste Phase-2-Daten deuten auf einen verbesserten Synapsenschutz.

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

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Weitere Artikel der Ausgabe 3/2020

Non-coding RNAs in Ischemic Stroke: Roles in the Neuroinflammation and Cell Death

Cell-Permeable Calpain Inhibitor SJA6017 Provides Functional Protection to Spinal Motoneurons Exposed to MPP+

Glutathione in Chlorpyrifos-and Chlorpyrifos-Oxon-Induced Toxicity: a Comparative Study Focused on Non-cholinergic Toxicity in HT22 Cells

Transcription Factors Phox2a/2b Upregulate Expression of Noradrenergic and Dopaminergic Phenotypes in Aged Rat Brains

The Role of Human LRRK2 in Methylmercury-Induced Inhibition of Microvesicle Formation of Cephalic Neurons in Caenorhabditis elegans