Neuroprotective effects of Mycoplasma hyorhinis against amyloid-β-peptide toxicity in SH-SY5Y human neuroblastoma cells are mediated by calpastatin upregulation in the mycoplasma-infected cells

Activity of neprilysin (NEP), the major protease which cleaves amyloid-β peptide (Aβ), is reportedly reduced in the brains of patients with Alzheimer’s disease (AD). Accumulation of Aβ generates reactive oxygen species (ROS) such as 4-hydroxynonenal (HNE), and then reduces activities of Aβ-degrading enzymes including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported to possess antioxidant and anti-inflammatory properties. The present study examined the effects of Xan on HNE- or oligomeric Aβ42-induced oxidative modification of NEP protein. Xan was added to the HNE- or oligomeric Aβ42-treated SK-N-SH human neuroblastoma cells and then levels, oxidative modification and enzymatic activities of NEP protein were measured. Increased HNE levels on NEP proteins and reduced enzymatic activities of NEP were observed in the HNE- or oligomeric Aβ42-treated cells. Xan reduced HNE levels on NEP proteins and preserved enzymatic activities of NEP in HNE- or oligomeric Aβ42-treated cells. Xan reduced Aβ42 accumulation and protected neurones against oligomeric Aβ42-induced neurotoxicity through preservation of NEP activities. These findings indicate that Xan possesses therapeutic potential for the treatment of neurodegenerative diseases, including AD, and suggest a potential mechanism for the neuroprotective effects of antioxidants for the prevention of AD.

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Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers

Frontiers in Neuroscience ◽

10.3389/fnins.2021.680026 ◽

2021 ◽

Vol 15 ◽

Author(s):

Ryan Limbocker ◽

Roxine Staats ◽

Sean Chia ◽

Francesco S. Ruggeri ◽

Benedetta Mannini ◽

...

Keyword(s):

Small Molecules ◽

Neuroblastoma Cells ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Human Neuroblastoma Cells ◽

Human Neuroblastoma ◽

Parkinson’S Diseases ◽

Wide Range ◽

Opposing Effects

The aberrant aggregation of proteins is a key molecular event in the development and progression of a wide range of neurodegenerative disorders. We have shown previously that squalamine and trodusquemine, two natural products in the aminosterol class, can modulate the aggregation of the amyloid-β peptide (Aβ) and of α-synuclein (αS), which are associated with Alzheimer’s and Parkinson’s diseases. In this work, we expand our previous analyses to two squalamine derivatives, des-squalamine and α-squalamine, obtaining further insights into the mechanism by which aminosterols modulate Aβ and αS aggregation. We then characterize the ability of these small molecules to alter the physicochemical properties of stabilized oligomeric species in vitro and to suppress the toxicity of these aggregates to varying degrees toward human neuroblastoma cells. We found that, despite the fact that these aminosterols exert opposing effects on Aβ and αS aggregation under the conditions that we tested, the modifications that they induced to the toxicity of oligomers were similar. Our results indicate that the suppression of toxicity is mediated by the displacement of toxic oligomeric species from cellular membranes by the aminosterols. This study, thus, provides evidence that aminosterols could be rationally optimized in drug discovery programs to target oligomer toxicity in Alzheimer’s and Parkinson’s diseases.

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Dose-dependent and sequence-sensitive effects of amyloid-β peptide on neurosteroidogenesis in human neuroblastoma cells

Neurochemistry International ◽

10.1016/j.neuint.2008.01.010 ◽

2008 ◽

Vol 52 (6) ◽

pp. 948-955 ◽

Cited By ~ 25

Author(s):

Véronique Schaeffer ◽

Laurence Meyer ◽

Christine Patte-Mensah ◽

Anne Eckert ◽

Ayikoe G. Mensah-Nyagan

Keyword(s):

Neuroblastoma Cells ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Human Neuroblastoma Cells ◽

Human Neuroblastoma ◽

Dose Dependent

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AMYLOID-β AND OXIDATIVE STRESS INDUCE INCREASED EXPRESSION OF APOLIPOPROTEIN E BY HUMAN NEUROBLASTOMA CELLS IN VITRO

Journal of Neuropathology & Experimental Neurology ◽

10.1097/00005072-199805000-00126 ◽

1998 ◽

Vol 57 (5) ◽

pp. 496

Author(s):

A. A. Golabek ◽

E. Kida ◽

M. Barcikowska ◽

H. M. Wisniewski

Keyword(s):

Oxidative Stress ◽

Apolipoprotein E ◽

Neuroblastoma Cells ◽

Amyloid Β ◽

Human Neuroblastoma Cells ◽

Human Neuroblastoma ◽

And Oxidative Stress

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Neuroprotective effects of mirtazapine and imipramine and their effect in pro- and anti-apoptotic gene expression in human neuroblastoma cells

Pharmacological Reports ◽

10.1007/s43440-019-00009-w ◽

2020 ◽

Vol 72 (3) ◽

pp. 563-570 ◽

Cited By ~ 1

Author(s):

Vicente Lieberknecht ◽

Daiane Engel ◽

Ana Lúcia S. Rodrigues ◽

Nelson H. Gabilan

Keyword(s):

Gene Expression ◽

Neuroblastoma Cells ◽

Human Neuroblastoma Cells ◽

Neuroprotective Effects ◽

Human Neuroblastoma ◽

Apoptotic Gene

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In vitroscreening of neuroprotective activity of Indian medicinal plantWithania somnifera

Journal of Nutritional Science ◽

10.1017/jns.2017.48 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 7

Author(s):

Manjeet Singh ◽

Charles Ramassamy

Keyword(s):

Neuroblastoma Cell ◽

Amyloid Β ◽

Acetylcholinesterase Activity ◽

Neuroprotective Activity ◽

Great Promise ◽

Human Neuroblastoma Cell ◽

Amyloid Β Peptide ◽

Aβ Peptide ◽

Neuroprotective Effects ◽

Human Neuroblastoma

AbstractCanine cognitive dysfunction (CCD) is an age-dependent neurodegenerative condition characterised by changes in decline in learning and memory patterns. The neurodegenerative features of CCD in ageing dogs and cats are similar to human ageing and Alzheimer's disease (AD). Discovering neuroprotective disease-modifying therapies against CCD and AD is a major challenge. Strong evidence supports the role of amyloid β peptide deposition and oxidative stress in the pathophysiology of CCD and AD. In both the human and canine brain, oxidative damage progressively increases with age. Dietary antioxidants from natural sources hold a great promise in halting the progression of CCD and AD.Withania somnifera(WS), an Ayurvedic tonic medicine, also known as ‘Indian ginseng’ orashwagandhahas a long history of use in memory-enhancing therapy but there is a dearth of studies on its neuroprotective effects. The objective of this study was to investigate whetherWSextract can protect against Aβ peptide- and acrolein-induced toxicity. We demonstrated that treatment withWSextract significantly protected the human neuroblastoma cell line SK-N-SH against Aβ peptide and acrolein in various cell survival assays. Furthermore, treatment withWSextract significantly reduced the generation of reactive oxygen species in SK-N-SH cells. Finally, our results showed thatWSextract is also a potent inhibitor of acetylcholinesterase activity. Thus, our initial findings indicate thatWSextract may act as an antioxidant and cholinergic modulator and may have beneficial effects in CCD and AD therapy.

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