Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death

Leong, Yong Qi; Ng, Khuen Yen; Chye, Soi Moi; Ling, Anna Pick Kiong; Koh, Rhun Yian

doi:10.1007/s11011-019-00516-y

Cited by 55 publications

(32 citation statements)

References 284 publications

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“…It is recognized that aberrant Aβ exhibits neurotoxicity that contributes to neuronal death, and this event is thought to be the primary factor that initiates the pathogenesis of AD [ 36 , 37 ]. Several neurotoxic effects of Aβ shown in the present study are consistent with previous studies [ 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

1,25(OH)2D3 Alleviates Aβ(25-35)-Induced Tau Hyperphosphorylation, Excessive Reactive Oxygen Species, and Apoptosis Through Interplay with Glial Cell Line-Derived Neurotrophic Factor Signaling in SH-SY5Y Cells

Lin

Chang

Kao

et al. 2020

IJMS

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Amyloid beta (Aβ) accumulation in the brain is one of the major pathological features of Alzheimer’s disease. The active form of vitamin D (1,25(OH)2D3), which acts via its nuclear hormone receptor, vitamin D receptor (VDR), has been implicated in the treatment of Aβ pathology, and is thus considered as a neuroprotective agent. However, its underlying molecular mechanisms of action are not yet fully understood. Here, we aim to investigate whether the molecular mechanisms of 1,25(OH)2D3 in ameliorating Aβ toxicity involve an interplay of glial cell line-derived neurotrophic factor (GDNF)-signaling in SH-SY5Y cells. Cells were treated with Aβ(25-35) as the source of toxicity, followed by the addition of 1,25(OH)2D3 with or without the GDNF inhibitor, heparinase III. The results show that 1,25(OH)2D3 modulated Aβ-induced reactive oxygen species, apoptosis, and tau protein hyperphosphorylation in SH-SY5Y cells. Additionally, 1,25(OH)2D3 restored the decreasing GDNF and the inhibited phosphorylation of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) protein expressions. In the presence of heparinase III, these damaging effects evoked by Aβ were not abolished by 1,25(OH)2D3. It appears 1,25(OH)2D3 is beneficial for the alleviation of Aβ neurotoxicity, and it might elicit its neuroprotection against Aβ neurotoxicity through an interplay with GDNF-signaling.

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Section: Discussionmentioning

confidence: 99%

1,25(OH)2D3 Alleviates Aβ(25-35)-Induced Tau Hyperphosphorylation, Excessive Reactive Oxygen Species, and Apoptosis Through Interplay with Glial Cell Line-Derived Neurotrophic Factor Signaling in SH-SY5Y Cells

Lin

Chang

Kao

et al. 2020

IJMS

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“…Iron not only aggravates toxic Aβ and hyperphosphorylated tau aggregation but also directly induces neuronal oxidative damage (Thirupathi and Chang, 2019). Considering the particularity and importance of iron in ferroptosis and the pathomechanism of AD, ferroptosis may provide a new insight into the molecular pathophysiology of the disease (Morris et al, 2018;Leong et al, 2019). Thus, future research aimed at validating the role of ferroptosis in AD is needed.…”

Section: Resultsmentioning

confidence: 99%

Iron Metabolism, Ferroptosis, and the Links With Alzheimer’s Disease

2020

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Iron is an essential transition metal for numerous biologic processes in mammals. Iron metabolism is regulated via several coordination mechanisms including absorption, utilization, recycling, and storage. Iron dyshomeostasis can result in intracellular iron retention, thereby damaging cells, tissues, and organs through free oxygen radical generation. Numerous studies have shown that brain iron overload is involved in the pathological mechanism of neurodegenerative disease including Alzheimer's disease (AD). However, the underlying mechanisms have not been fully elucidated. Ferroptosis, a newly defined iron-dependent form of cell death, which is distinct from apoptosis, necrosis, autophagy, and other forms of cell death, may provide us a new viewpoint. Here, we set out to summarize the current knowledge of iron metabolism and ferroptosis, and review the contributions of iron and ferroptosis to AD.

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“…Moreover, neurodegenerative diseases are multifactorial and many pathways must be considered (Kuang et al, 2019). Therefore, not only autophagy but also necrosis and apoptosis contributed to neuronal cell death (Leong et al, 2020). Remarkably, natural compounds able to limit neurodegeneration in vitro might not be effective in vivo and multiple products are suggested both natural and synthetic (Mazzanti and Di Giacomo, 2016).…”

Section: Resultsmentioning

confidence: 99%

Natural Compounds and Autophagy: Allies Against Neurodegeneration

Stacchiotti

Corsetti

2020

Front. Cell Dev. Biol.

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Prolonging the healthy life span and limiting neurological illness are imperative goals in gerontology. Age-related neurodegeneration is progressive and leads to severe diseases affecting motility, memory, cognitive function, and social life. To date, no effective treatments are available for neurodegeneration and irreversible neuronal loss. Bioactive phytochemicals could represent a natural alternative to ensure active aging and slow onset of neurodegenerative diseases in elderly patients. Autophagy or macroautophagy is an evolutionarily conserved clearing process that is needed to remove aggregateprone proteins and organelles in neurons and glia. It also is crucial in synaptic plasticity. Aberrant autophagy has a key role in aging and neurodegeneration. Recent evidence indicates that polyphenols like resveratrol and curcumin, flavonoids, like quercetin, polyamine, like spermidine and sugars, like trehalose, limit brain damage in vitro and in vivo. Their common mechanism of action leads to restoration of efficient autophagy by dismantling misfolded proteins and dysfunctional mitochondria. This review focuses on the role of dietary phytochemicals as modulators of autophagy to fight Alzheimer's and Parkinson's diseases, fronto-temporal dementia, amyotrophic lateral sclerosis, and psychiatric disorders. Currently, most studies have involved in vitro or preclinical animal models, and the therapeutic use of phytochemicals in patients remains limited.

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Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death

Cited by 55 publications

References 284 publications

1,25(OH)2D3 Alleviates Aβ(25-35)-Induced Tau Hyperphosphorylation, Excessive Reactive Oxygen Species, and Apoptosis Through Interplay with Glial Cell Line-Derived Neurotrophic Factor Signaling in SH-SY5Y Cells

1,25(OH)2D3 Alleviates Aβ(25-35)-Induced Tau Hyperphosphorylation, Excessive Reactive Oxygen Species, and Apoptosis Through Interplay with Glial Cell Line-Derived Neurotrophic Factor Signaling in SH-SY5Y Cells

Iron Metabolism, Ferroptosis, and the Links With Alzheimer’s Disease

Natural Compounds and Autophagy: Allies Against Neurodegeneration

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