Role of methionine 35 in the intracellular Ca2+homeostasis dysregulation and Ca2+-dependent apoptosis induced by amyloid β-peptide in human neuroblastoma IMR32 cells

Increased production of amyloid β-peptide (Aβ) and altered processing of tau in Alzheimer's disease (AD) are associated with synaptic dysfunction, neuronal death and cognitive and behavioural deficits. Neuroinflammation is also a prominent feature of AD brain and considerable evidence indicates that inflammatory events play a significant role in modulating the progression of AD. The role of microglia in AD inflammation has long been acknowledged. Substantial evidence now demonstrates that astrocyte-mediated inflammatory responses also influence pathology development, synapse health and neurodegeneration in AD. Several anti-inflammatory therapies targeting astrocytes show significant benefit in models of disease, particularly with respect to tau-associated neurodegeneration. However, the effectiveness of these approaches is complex, since modulating inflammatory pathways often has opposing effects on the development of tau and amyloid pathology, and is dependent on the precise phenotype and activities of astrocytes in different cellular environments. An increased understanding of interactions between astrocytes and neurons under different conditions is required for the development of safe and effective astrocyte-based therapies for AD and related neurodegenerative diseases.

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In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid β-peptide of APP

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2009.10.035 ◽

2010 ◽

Vol 48 (1) ◽

pp. 136-144 ◽

Cited By ~ 122

Author(s):

D. Allan Butterfield ◽

Veronica Galvan ◽

Miranda Bader Lange ◽

Huidong Tang ◽

Renã A. Sowell ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer Disease ◽

Transgenic Mice ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Methionine 35

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2P048 Role of the hydrophobia C-terminal region in lipid membrane-induced secondary structure formation of amyloid-β peptide(Proteins-structure and structure-function relationship,Oral Presentations)

Seibutsu Butsuri ◽

10.2142/biophys.47.s125_1 ◽

2007 ◽

Vol 47 (supplement) ◽

pp. S125

Author(s):

Mayumi Yoda ◽

Takashi Miura ◽

Hideo Takeuchi

Keyword(s):

Secondary Structure ◽

Structure Function ◽

Structure Formation ◽

Lipid Membrane ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Secondary Structure Formation ◽

Function Relationship ◽

Oral Presentations

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The antioxidant xanthorrhizol prevents amyloid-β-induced oxidative modification and inactivation of neprilysin

Bioscience Reports ◽

10.1042/bsr20171611 ◽

2018 ◽

Vol 38 (1) ◽

Cited By ~ 6

Author(s):

Chol Seung Lim ◽

Jung-Soo Han

Keyword(s):

Therapeutic Potential ◽

Neuroblastoma Cells ◽

Amyloid Β ◽

Enzymatic Activities ◽

Oxidative Modification ◽

Amyloid Β Peptide ◽

Oxygen Species ◽

Human Neuroblastoma Cells ◽

Neuroprotective Effects ◽

Human Neuroblastoma

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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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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