Evidence for the Involvement of Apoptosis-Inducing Factor–Mediated Caspase-Independent Neuronal Death in Alzheimer Disease

Yu, Wenbin; Mechawar, Naguib; Krantic, Slavica; Quirion, Rémi

doi:10.2353/ajpath.2010.090496

Cited by 49 publications

(30 citation statements)

References 61 publications

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“…Oxidative stress contributes to apoptosis through both extrinsic pathway and intrinsic pathway. Oxidative-induced apoptosis potentially contribute to Ab generation (Roth 2001;Yu et al 2010). The Ab generation is the process of two sequential cleavages of the APP by two proteolytic enzymes: b-secretase and c-secretase.…”

Section: Abbreviationsmentioning

confidence: 99%

Oxidative Stress and β-Amyloid Protein in Alzheimer’s Disease

2011

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Oxidative stress has been proposed to be an important factor in the pathogenesis of Alzheimer's disease (AD) and contributed to β-amyloid (Aβ) generation. Interaction between oxidative stress and neuro-inflammation leads to Aβ generation. AD is associated with an increase in blood-brain barrier (BBB) permeability due to tight junction involvement. Oxidative stress decreases the expression of low-density lipoprotein receptor-related protein 1 and up-regulates receptor for advanced glycation end products in BBB and increases the BBB permeability, which could potentially lead to increased deposition of Aβ within AD brain. Apoptosis takes place in the pathogenesis of AD, and oxidative stress contributes to apoptosis through both extrinsic pathway and intrinsic pathway. Oxidative stress-induced apoptosis may be a potential factor to Aβ generation. Aβ generation requires two sequential cleavages of APP, with the two proteolytic enzymes: β-secretase and γ-secretase. Oxidative damage up-regulates Aβ via inducing activity of β- and γ-secretases. In this review, we will focus on the mechanism and pathway that oxidative stress contributes to Aβ generation.

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Section: Abbreviationsmentioning

confidence: 99%

Oxidative Stress and β-Amyloid Protein in Alzheimer’s Disease

2011

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“…Increasing evidence suggests that caspase-independent pathways play a critical role in neuronal death and AIF is emerging as a predominate mediator [16,17] . Although GM-induced cell death is thought to be triggered by apoptotic reactions, the exact mechanisms are not well understood.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis-Inducing Factor Is Involved in Gentamicin-Induced Vestibular Hair Cell Death

Zhang¹,

Fan²,

Han³

et al. 2011

ORL

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Aim: Vestibular hair cell loss in response to different stimuli may be attributable to the occurrence of apoptosis, in which apoptosis-inducing factor (AIF) is an important regulator mediating apoptotic process independent of caspases. This study was designed to investigate the possible involvement of AIF in gentamicin (GM)-induced vestibular hair cell death. Methods: Vestibular organs from postnatal day 3 or 4 rats were maintained in tissue culture and were exposed to 2 mg/ml GM for up to 72 h. Vestibular hair cell viability was quantified by MTT assay. Apoptosis was determined by flow cytometry. AIF activation was examined by RT-PCR. The expressions of the mitochondrial protein and cytoplasm protein of AIF were detected by Western blot. Results: GM could significantly inhibit the cell viability of vestibular hair cells in a dose- and time-dependent manner. The number of apoptotic cells treated with GM was higher than that of cells not treated with GM. RT-PCR showed upregulation of AIF mRNA under GM. Western blot showed that AIF from mitochondria was decreased, whereas AIF from cytoplasm was increased after GM exposure. Conclusions: AIF participates in GM-induced apoptosis of vestibular hair cells.

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“…This hypothesis states that progressive accumulation of intracellular and extracellular Aß aggregates plays a fundamental role in neurodegeneration observed in AD. It has been suggested that Aß-induced neuronal death is related to different programmed cell death (PCD) pathways; a caspase-dependent apoptotic PCD [3,4] and apoptosis inducing factor (AIF)-mediated, caspase-independent PCD [5][6][7] pathway. The involvement of classical (caspase-dependent) apoptosis is generally recognized [3] but morphological studies of Aß-treated neuronal cell cultures [4], animal models [5] and post-mortem human brain tissues [6,7] suggest a role of additional non-apoptotic (caspase-independent) cell death.…”

Section: Introductionmentioning

confidence: 99%

Possible Involvement of Programmed Cell Death Pathways in the Neuroprotective Action of Polyphenols

Bastianetto¹,

Krantic²,

Chabot³

et al. 2011

CAR

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One of the hallmarks of Alzheimer's disease is the accumulation of senile plaques composed of extra-cellular aggregates of beta-amyloid (Aβ) peptides. It is well established that at least in vitro, Aβ triggers apoptotic cell death via the activation of caspase-dependent and -independent cell death effectors, namely caspase-3 and apoptosis inducing factor (AIF), respectively. Epidemiological studies have reported that elderly people have a lower risk (up to 50%) of developing dementia if they regularly eat fruits and vegetables and drink tea and red wine (in moderation). Numerous studies indicate that polyphenols derived from these foods and beverages account for the observed neuroprotective effects. In particular, we have reported that polyphenols extracted from green tea (i.e. epigallocatechin gallate or EGCG) and red wine (i.e. resveratrol) block Aβ-induced hippocampal cell death, by at least partially inhibiting Aβ fibrillisation. It has been shown that polyphenols may also modulate caspase-dependent and -independent programmed cell death (PCD) pathways. Indeed, polyphenols including resveratrol, EGCG and luteolin significantly inhibit the activation of the key apoptotic executioner, caspase-3 and are able to modulate mitogen-activated protein kinases known to play an important role in neuronal apoptosis. Moreover, it has been reported that polyphenols may exert their anti-apoptotic action by inhibiting AIF release from mitochondria, thus providing new mechanism of action for polyphenols. This review aims to update the current knowledge regarding the differential effects of polyphenols on PCD pathways and discuss their putative neuroprotective action resulting from their capacity to modulate these pathways.

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Evidence for the Involvement of Apoptosis-Inducing Factor–Mediated Caspase-Independent Neuronal Death in Alzheimer Disease

Cited by 49 publications

References 61 publications

Oxidative Stress and β-Amyloid Protein in Alzheimer’s Disease

Oxidative Stress and β-Amyloid Protein in Alzheimer’s Disease

Apoptosis-Inducing Factor Is Involved in Gentamicin-Induced Vestibular Hair Cell Death

Possible Involvement of Programmed Cell Death Pathways in the Neuroprotective Action of Polyphenols

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