Acrolein induces Alzheimer's disease-like pathologies in vitro and in vivo

Huang, Yingjuan; Jin, Minghua; Pi, Rongbiao; Zhang, Junjie; Ouyang, Ying; Chao, Xiaojuan; Chen, Mei-Hui; Liu, Peiqing; Yu, Jing; Ramassamy, Charles; Dou, Jingtao; Chen, Xiaohong; Jiang, Yiming; Qin, Jian

doi:10.1016/j.toxlet.2012.12.023

Cited by 74 publications

(46 citation statements)

References 49 publications

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“…Addition of Aβ 1-42 peptide to HT22 cells induced cell death as well as a previous report [18]. Crocetin has been known to have potent anti-oxidant [19], anti-cancer [9], and anti-inflammation activities [8].…”

Section: Discussionsupporting

confidence: 71%

Crocetin Prevents Amyloid β1-42-Induced Cell Death in Murine Hippocampal Cells

Yoshino¹,

Ishisaka²,

Umigai³

et al. 2014

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Crocetin is an aglycon of carotenoid extracted by saffron stigmas (Crocus sativus L.) and known to have a potent anti-oxidative effect. Amyliod β (Aβ), hallmark of Alzheimer's disease, is reported to have neurotoxicity partly via oxidative stress. In this study, we investigated the effect of crocetin on hippocampal HT22 cell death induced by Aβ 1-42 . Furthermore, to clarify the mechanism underlying the protective effects of crocetin against Aβ 1-42 -induced cell death, we measured reactive oxygen species (ROS) production by CM-H 2 DCFDA kit assay. Crocetin at 1 -10 μM protected HT22 cells against Aβ 1-42 -induced neuronal cell death and decreased ROS production increased by Aβ 1-42 . These results that crocetin has the potent neuroprotective effect against Aβ 1-42 -induced cytotoxicity in hippocampal cells by attenuating oxidative stress, suggest that crocetin may provide a useful therapeutic strategy against Aβ-related disorders.

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Section: Discussionsupporting

confidence: 71%

Crocetin Prevents Amyloid β1-42-Induced Cell Death in Murine Hippocampal Cells

Yoshino¹,

Ishisaka²,

Umigai³

et al. 2014

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“…Furthermore, acrolein-induced apoptosis was verified by activating caspase 3 and caspase 7 as well as forming DNA laddering, biomarkers of apoptosis2324. Many in vivo studies have demonstrated the acrolein-induced neurotoxicity in Alzheimer’s disease and spinal cord injury102526. In contrast, few in vivo studies have focused on the neurotoxic mechanisms of acrolein in the etiology of Parkinsonism.…”

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confidence: 99%

Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death

Wang¹,

Lin²,

Zhao³

et al. 2017

Sci Rep

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Clinical studies report significant increases in acrolein (an α,β-unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson’s disease (PD). In the present study, acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system was investigated by local infusion of acrolein (15, 50, 150 nmoles/0.5 μl) in the SN of Sprague-Dawley rats. Acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was delineated by reductions in tyrosine hydroxylase (TH) levels, dopamine transporter levels and TH-positive neurons in the infused SN as well as in striatal dopamine content. At the same time, apomorphine-induced turning behavior was evident in rats subjected to a unilateral infusion of acrolein in SN. Acrolein was pro-oxidative by increasing 4-hydroxy-2-nonenal and heme oxygenase-1 levels. Furthermore, acrolein conjugated with proteins at lysine residue and induced α-synuclein aggregation in the infused SN. Acrolein was pro-inflammatory by activating astrocytes and microglia. In addition, acrolein activated caspase 1 in the infused SN, suggesting acrolein-induced inflammasome formation. The neurotoxic mechanisms underlying acrolein-induced neurotoxicity involved programmed cell death, including apoptosis and necroptosis. Compared with well-known Parkinsonian neurotoxins, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and rotenone which do not exist in the SN of PD patients, our in vivo study shows that acrolein acts as a Parkinsonian neurotoxin in the nigrostriatal dopaminergic system of rat brain.

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“…17 In addition to accumulating, they may also covalently modify proteins, alter glial cell function, 68,69 or induce an inflammatory response, one or more of which may cause the kind of slowly progressive neuronal loss that is characteristic of AD. 63,64 …”

Section: Discussionmentioning

confidence: 99%

Amyloid Plaque-Associated Oxidative Degradation of Uniformly Radiolabeled Arachidonic Acid

Furman

Murray

Schall

et al. 2016

ACS Chem. Neurosci.

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Oxidative stress is a frequently observed feature of Alzheimer's disease, but its pathological significance is not understood. To explore the relationship between oxidative stress and amyloid plaques, uniformly radiolabeled arachidonate was introduced into transgenic mouse models of Alzheimer's disease via intracerebroventricular injection. Uniform labeling with carbon-14 is used here for the first time, and made possible meaningful quantification of arachidonate oxidative degradation products. The injected arachidonate entered a fatty acid pool that was subject to oxidative degradation in both transgenic and wild type animals. However, the extent of its degradation was markedly greater in the hippocampus of transgenic animals where amyloid plaques were abundant. In human Alzheimer's brain, plaque-associated proteins were post-translationally modified by hydroxynonenal, a well-known oxidative degradation product of arachidonate. These results suggest that several recurring themes in Alzheimer's pathogenesis, amyloid β proteins, transition metal ions, oxidative stress, and apolipoprotein isoforms, may be involved in a common mechanism that has the potential to explain both neuronal loss and fibril formation in this disease.

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Acrolein induces Alzheimer's disease-like pathologies in vitro and in vivo

Cited by 74 publications

References 49 publications

Crocetin Prevents Amyloid <i>β</i><sub>1-42</sub>-Induced Cell Death in Murine Hippocampal Cells

Crocetin Prevents Amyloid <i>β</i><sub>1-42</sub>-Induced Cell Death in Murine Hippocampal Cells

Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death

Amyloid Plaque-Associated Oxidative Degradation of Uniformly Radiolabeled Arachidonic Acid

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Acrolein induces Alzheimer's disease-like pathologies in vitro and in vivo

Cited by 74 publications

References 49 publications

Crocetin Prevents Amyloid &lt;i&gt;β&lt;/i&gt;&lt;sub&gt;1-42&lt;/sub&gt;-Induced Cell Death in Murine Hippocampal Cells

Crocetin Prevents Amyloid &lt;i&gt;β&lt;/i&gt;&lt;sub&gt;1-42&lt;/sub&gt;-Induced Cell Death in Murine Hippocampal Cells

Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death

Amyloid Plaque-Associated Oxidative Degradation of Uniformly Radiolabeled Arachidonic Acid

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Crocetin Prevents Amyloid <i>β</i><sub>1-42</sub>-Induced Cell Death in Murine Hippocampal Cells

Crocetin Prevents Amyloid <i>β</i><sub>1-42</sub>-Induced Cell Death in Murine Hippocampal Cells