Multiple caspases are involved in ?-amyloid-induced neuronal apoptosis

Allen, Jason W.; Eldadah, Basil A.; Huang, Xian; Knoblach, Susan M.; Faden, Alan I.

doi:10.1002/jnr.1126

Cited by 120 publications

(87 citation statements)

References 33 publications

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“…[10][11][12][13][14] We therefore investigated the effect of 12-LOX downregulation on Ab-induced caspase activation. As shown in Figure 2, treatment of cortical cells with 25 mM Ab led to the activation of caspase-2, -3 and -8.…”

Section: Resultsmentioning

confidence: 99%

“…When combining these data to those previously obtained with the 12-LOX inhibitor, it thus appears that protection against neuronal death induced by Ab could be achieved upon blockade of 12-LOX through either inhibition of the enzyme or downregulation of its expression. Moreover, it is now well documented that caspases participate in Ab-induced apoptosis, [10][11][12][13] and that their activation correlates with apoptotic features in AD brains. 53,54 In particular, caspase-2, -3 and -8 have been reported to be activated in neurons following Ab treatment.…”

Section: Discussionmentioning

confidence: 99%

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Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

et al. 2004

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The cyclo-oxygenase (COX) and lipoxygenase (LOX) pathways belong to the eicosanoid synthesis pathway, a major component of the chronic inflammatory process occurring in Alzheimer's disease (AD). Clinical studies reported beneficial effects of COX inhibitors, but little is known about the involvement of LOXs in AD pathogenesis. b-amyloid peptide (Ab) accumulation contributes to neurodegeneration in AD, but mechanisms underlying Ab toxicity have not been fully elucidated yet. Here, using an antisense oligonucleotide-based strategy, we show that blockade of 12-LOX expression prevents both Ab-induced apoptosis and overexpression of c-Jun, a factor required for the apoptotic process, in cortical neurons. Conversely, the 12-LOX metabolite, 12(S)-HETE (12(S)-hydroxy-(5Z, 8Z, 10E, 14Z)-eicosatetraenoic acid), promoted c-Jun-dependent apoptosis. Specificity of the 12-LOX involvement was further supported by the observed lack of contribution of 5-LOX in this process. These data indicate that blockade of 12-LOX expression disrupts a c-Jun-dependent apoptosis pathway, and suggest that 12-LOX may represent a new target for the treatment of AD.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

et al. 2004

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“…Furthermore, the Aβ-induced apoptotic cell death in PC12 cells is associated with the decreased expression of the anti-apoptotic molecule Bcl-2 and the increased expression of the pro-apoptotic molecule Bax (Xiao et al, 2002;Yuyama et al, 2003). The activation of caspase-3 plays a role in Aβ-induced apoptosis (Allen et al, 2001) and an increase in activated caspase-3 has been reported in AD brains (Su et al, 2001). Therefore, the decrease in Bax or active caspase-3 expression and increase in Bcl-2 expression can provide a neuroprotective effect by inhibiting Aβ-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…The apoptotic cell death induced by Aβ is also associated with the neuritic degeneration and the onset of AD (Loo et al, 1993;Selkoe, 2000). In addition, the activation of caspase-3 plays a role in Aβ-induced apoptosis (Allen et al, 2001) and an increase in activated caspase-3 has been reported in AD brains (Su et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Chlorogenic Acid against Aβ-Induced Neurotoxicity

Lee¹,

Won²,

Kim³

et al. 2011

Biomolecules and Therapeutics

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Beta-amyloid (Aβ) is considered as one of the major causes of Alzheimer's disease. This study examined the neuroprotective effects of chlorogenic acid, a naturally occurring polyphenol which is distributed widely in plants, fruits and vegetables, against Aβ-induced toxicity. Aβ decreased signifi cantly the viability of PC12 cells. This was accompanied by an increase in the intracellular calcium levels and cleaved caspase-3. In addition, Aβ induced an increase in Bax, and a decrease in Bcl-2 compared to the controls. However, a pre-treatment with chlorogenic acid rescued the PC12 cells from Aβ by attenuating the elevated intracellular calcium levels and reducing the levels of the apoptosis related proteins, including caspase-3, Bcl-2 and Bax. These results suggest that the protective effects of chlorogenic acid are, at least in parts, by attenuating the intracellular calcium infl ux and reducing apoptosis induced by Aβ. Abstractthat is distributed widely in plants, fruits and vegetables, such as coffee beans, potatoes and apples (Clifford, 1999;Zang et al., 2003). It possesses a wide range of biological activities including anti-carcinogenic, anti-bacterial, anti-infl ammatory and antioxidant activities in vitro (Huang et al., 1988;Almeida et al., 2006;dos Santos et al., 2006). However, the possible benefi cial effects of chlorogenic acid against Aβ have not been elucidated. Therefore, this study evaluated the neuroprotective effects of chlorogenic acid against Aβ-induced toxicity in PC12 cells (rat pheochromocytoma). To accomplish this, an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was carried out to determine if chlorogenic acid protected the PC12 cells against Aβ. To examine their underlying mechanisms, the effects of chlorogenic acid on the intracellular calcium level and apoptosis related proteins including Bcl-2, Bax and caspase-3 were evaluated as possible neuroprotective mechanisms against Aβ.

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“…However, the experiments performed using caspase-3 inhibitors suggested that this caspase might also play a role in the generation of this fragment. A growing body of evidence suggests that caspases play a pivotal role in apoptosis induced by A␤ (Ivins et al, 1998(Ivins et al, , 1999Troy et al, 2000;Allen et al, 2001;Marques et al, 2003). Especially, caspase-3 is considered a key component of A␤-induced apoptosis in cultured neurons (Harada and Sugimoto, 1999;Marin et al, 2000;Allen et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

The Generation of a 17 kDa Neurotoxic Fragment: An Alternative Mechanism by which Tau Mediates β-Amyloid-Induced Neurodegeneration

Park¹,

Ferreira²

2005

J. Neurosci.

238

251

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Recently, we have shown that the microtubule-associated protein tau is essential for ␤-amyloid (A␤)-induced neurotoxicity in hippocampal neurons. However, the mechanisms by which tau mediates A␤-induced neurite degeneration remain poorly understood. In the present study, we analyzed whether tau cleavage played a role in these events. Our results showed that pre-aggregated A␤ induced the generation of a 17 kDa tau fragment in cultured hippocampal neurons. The generation of this fragment was preceded by the activation of calpain-1. Conversely, inhibitors of this protease, but not of caspases, completely prevented tau proteolysis leading to the generation of the 17 kDa fragment and significantly reduced A␤-induced neuronal death. Furthermore, the expression of this fragment in cultured hippocampal neurons induced the formation of numerous varicosity-bearing tortuous processes, as well as the complete degeneration of some of those neurite processes. These results suggest that A␤-induced neurotoxicity may be mediated, at least in part, through the calpain-mediated generation of a toxic 17 kDa tau fragment. Collectively, these results provide insight into a novel mechanism by which tau could mediate A␤-induced neurotoxicity.

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Multiple caspases are involved in ?-amyloid-induced neuronal apoptosis

Cited by 120 publications

References 33 publications

Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

Protective Effect of Chlorogenic Acid against Aβ-Induced Neurotoxicity

The Generation of a 17 kDa Neurotoxic Fragment: An Alternative Mechanism by which Tau Mediates β-Amyloid-Induced Neurodegeneration

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