Molecular mechanism of neurodegeneration induced by Alzheimer’s β-amyloid protein: channel formation and disruption of calcium homeostasis

Kawahara, Masahiro; Kuroda, Yoichiro

doi:10.1016/s0361-9230(00)00370-1

Cited by 208 publications

(154 citation statements)

References 58 publications

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“…There is evidence for a complex interaction between Ab and calcium. Released Ab has been suggested to be incorporated into neuronal membranes forming calcium-permeable channels (Bhatia et al, 2000;Kawahara and Kuroda, 2000), which would allow uncontrolled calcium influx elevating intracellular calcium concentrations. This is hypothesized to be one of the mechanisms of the neurotoxicity of Ab peptides.…”

Section: Discussionmentioning

confidence: 99%

Coaccumulation of Calcium and β-Amyloid in the Thalamus after Transient Middle Cerebral Artery Occlusion in Rats

Mäkinen¹,

Groen

Clarke

et al. 2007

J Cereb Blood Flow Metab

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Transient occlusion of the middle cerebral artery (MCAO) in rats leads to abnormal accumulation of b-amyloid (Ab) peptides in the thalamus. This study investigated the chemical composition of these deposits. Adult male human b-amyloid precursor protein (APP) overexpressing (hAPP695) rats and their wild-type littermates were subjected to transient MCAO for 2 h or sham operation. After 26-week survival time, histological examination revealed an overlapping distribution pattern for rodent and human Ab in the thalamus of hAPP695 rats subjected to MCAO. X-ray microanalysis showed that the deposits did not contain significant amount of iron, zinc, or copper typical to senile plaques. In contrast, the deposit both in hAPP695 and non-transgenic rats contained calcium and phosphorus in a ratio (1.2860.15) characteristic to hydroxyapatites. Alizarin red staining confirmed that calcium coaccumulated in these Ab deposits. It is suggested that APP expression is induced by ischemic insult in cortical neurons adjacent to infarct, which in turn is reflected as increased release of Ab peptides by their corticothalamic axon endings. This together with insufficient clearance or atypical degradation of Ab peptides lead to dysregulation of calcium homeostatis and coaccumulation in the thalamus.

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Section: Discussionmentioning

confidence: 99%

Coaccumulation of Calcium and β-Amyloid in the Thalamus after Transient Middle Cerebral Artery Occlusion in Rats

Mäkinen¹,

Groen

Clarke

et al. 2007

J Cereb Blood Flow Metab

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show abstract

“…The beta-amyloid peptide (Aβ) is a protein that is produced in excessive quantities and accumulates in the form of senile plaque in Alzheimer's disease (AD) (Kawahara and Kuroda, 2000). The sequential proteolysis of the amyloid precursor protein (APP) by β-and γ-secretases to Aβ and self-aggregation of Aβ monomers to oligomers are some of the characteristics found in AD (Selkoe, 1998;Lue et al, 1999).…”

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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“…1) Neurofibrillary tangles (NFTs), which are comprised of intracellular aggregates of hyperphosphorylated tau, are another pathological hallmark of AD. 2,3) Neurotoxicity, oxidative damage, and inflammation induced by A oligomers are considered to be one of the major causes of Alzheimer's disease.…”

mentioning

confidence: 99%

“…The A (25-35) used in this study was pre-aggregated prior to use in a 37 C water bath for 3 d. For the MTT assay, PC12 cells cultured in DMEM þ 15% horse serum þ 5% fetal bovine serum (4 Â 10 4 cells per well) were plated in 96-well tissue culture plates, after which the cells were pretreated with various concentrations of delphinidin (1,4,20, and 100 mg/ml) for 1 h. The cells were then incubated with 10 mM A (25-35) for an additional 24 h, after which MTT solution (10 ml per well, 5 mg/ml stock solution in PBS) was added over 3 h at 37 C. The cells were then lysed in the presence of 100 ml of lysis buffer (10% w/v of SDS in 0.01 N HCl) overnight at 37 C. Next the optical density of the resulting solutions was colorimetrically determined at 570 nm using a microplate reader (Molecular Devices, Sunnywale, CA). For Trypan blue assay, PC12 cells treated with A in the presence and the absence of delphinidin were collected by centrifugation and incubated with Trypan blue solution at 37 C for 10 min, after which the numbers of viable cells and stained cells were counted under an inverted microscope (Optica, Boston, MA).…”

mentioning

confidence: 99%

Delphinidin Ameliorates Beta-Amyloid-Induced Neurotoxicity by Inhibiting Calcium Influx and Tau Hyperphosphorylation

Kim

Sul

Lim

et al. 2009

Bioscience, Biotechnology, and Biochemistry

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Molecular mechanism of neurodegeneration induced by Alzheimer’s β-amyloid protein: channel formation and disruption of calcium homeostasis

Cited by 208 publications

References 58 publications

Coaccumulation of Calcium and β-Amyloid in the Thalamus after Transient Middle Cerebral Artery Occlusion in Rats

Coaccumulation of Calcium and β-Amyloid in the Thalamus after Transient Middle Cerebral Artery Occlusion in Rats

Protective Effect of Chlorogenic Acid against Aβ-Induced Neurotoxicity

Delphinidin Ameliorates Beta-Amyloid-Induced Neurotoxicity by Inhibiting Calcium Influx and Tau Hyperphosphorylation

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