Acetylcholinesterase provides deeper insights into Alzheimer's disease

Shen, Zheng-Xuan

doi:10.1016/0306-9877(94)90045-0

Cited by 23 publications

(11 citation statements)

References 69 publications

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“…However, both of these elements were found to decrease amyloid toxicity in culture (Oda et al, 1995;Boggs et al, 1996;Puttfarcken et al, 1997), suggesting that an adequate balance between toxic elements and the microenvironment defines the final toxicity of A␤ fibrils. In this context, it is interesting to mention that the potential role of AChE in AD is further supported by the fact that AChE systems, in particular those more vulnerable to AD such as the lightly stained neurons located in the entorhinal cortex, the CA1 and subiculum of the hippocampus, and the amygdala (Shen, 1994, Kasa et al, 1997, are the first to be affected in the pathological process of AD. Although the cellular mechanism of action of A␤ is not precisely understood, several processes have been proposed.…”

Section: Ache-a␤ Complexes Increase the Neurotoxicity Of Alzheimer's mentioning

confidence: 99%

Stable Complexes Involving Acetylcholinesterase and Amyloid-β Peptide Change the Biochemical Properties of the Enzyme and Increase the Neurotoxicity of Alzheimer’s Fibrils

et al. 1998

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Brain acetylcholinesterase (AChE) forms stable complexes with amyloid-␤ peptide (A␤) during its assembly into filaments, in agreement with its colocalization with the A␤ deposits of Alzheimer's brain. The association of the enzyme with nascent A␤ aggregates occurs as early as after 30 min of incubation. Analysis of the catalytic activity of the AChE incorporated into these complexes shows an anomalous behavior reminiscent of the AChE associated with senile plaques, which includes a resistance to low pH, high substrate concentrations, and lower sensitivity to AChE inhibitors. Furthermore, the toxicity of the AChE-amyloid complexes is higher than that of the A␤ aggregates alone. Thus, in addition to its possible role as a heterogeneous nucleator during amyloid formation, AChE, by forming such stable complexes, may increase the neurotoxicity of A␤ fibrils and thus may determine the selective neuronal loss observed in Alzheimer's brain.

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Section: Ache-a␤ Complexes Increase the Neurotoxicity Of Alzheimer's mentioning

confidence: 99%

Stable Complexes Involving Acetylcholinesterase and Amyloid-β Peptide Change the Biochemical Properties of the Enzyme and Increase the Neurotoxicity of Alzheimer’s Fibrils

et al. 1998

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“…13,14 First, an important characteristic of the neurons that degenerate in AD seems to be the expression of AChE independent of whether they are cholinergic or not. 29 Second, most of the cortical AChE activity present in AD brain is found associated with senile plaques, 18,27 which in turn are related to neuronal degeneration. 8 Third, it has been reported that AChE is able to promote the aggregation of the A␤ peptide, 12 a condition that increases the A␤ toxicity.…”

Section: Figurementioning

confidence: 99%

“…It is possible that components of senile plaques other than A␤ are involved in this selective neuronal cell death and AChE is one such candidate. In fact, among the neurons that degenerate in AD, there are populations that do not contain choline acetyltransferase yet still express AChE, 29,30 suggesting that a major characteristic of degenerative neurons could be the expression of AChE. 11,30 Furthermore, most of the cortical AChE activity present in AD brain has been found associated with senile plaques, where it co-localizes with A␤ deposits probably promoting the aggregation of A␤ into amyloid fibrils, thus increasing its toxicity.…”

Section: Introductionmentioning

confidence: 99%

Toxic effects of acetylcholinesterase on neuronal and glial-like cells in vitro

et al. 1998

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Acetylcholinesterase (AChE), the enzyme involved in the hydrolysis of the neurotransmitter acetylcholine, has been implicated in non-cholinergic actions which may play a role in neurodegenerative diseases such as Alzheimer's disease. To study the potential cytotoxicity of brain AChE, the effects of affinity purified AChE were analyzed on neuronal (Neuro 2a) and glial-like (B12) cells. LDH release and MTT reduction assays showed that AChE was toxic; the toxicity was dependent on the enzyme concentration, time of incubation and cellular density. The toxic effect of AChE was not related to its catalytic activity, since the anti-cholinesterase drug BW284C51 and heat inactivation were unable to block the effects of the enzyme. When cells were incubated at 4؇C, toxicity was completely blocked, in contrast to cells incubated at 37؇C. The presence of serum in the culture medium inhibited the toxic effects of AChE. Cytoplasmic shrinkage, condensation and fragmentation of nucleus as well as DNA strand breaks detected with the TUNEL technique indicated that apoptotic cell death is involved in the effect of AChE. Considering that we have previously shown that AChE promotes the assembly of ␤-amyloid peptide into neurotoxic amyloid fibrils, it is conceivable that the neurotoxicity of AChE shown here may play a role in the neuronal degeneration observed in Alzheimer's disease.

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“…It has been indicated that acetylcholinesterase may also play an important role in the pathogenesis of AD (15). The lowest activity of AChE was reported as a sign of the most severe stages of dementia.…”

Section: Discussionmentioning

confidence: 99%

Acetylcholinesterase Activity in the Mongolian Gerbil Brain after Acute Poisoning with Aluminum

Micić

Petronijević

2000

JAD

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ABSTRACT:The aim of the present study was to evaluate the acetylcholinesterase activity in the brain of adult gerbils (Meriones unguiculatus) treated with aluminum. AlCl 3 x 6H 2 O was given "per os" in the amount of 3.7 g/kg body weight. The animals were killed 24, 48, 72 and 96 hours after the treatment. The activities of acetylholinesterase in the mitochondrial and microsomal fractions of cortex, hippocampus and thalamus as well as plasma levels of aluminum were measured. Acetylcholinesterase activity was significantly reduced in the mitochondrial and microsomal fraction of all investigated structures. Decrease of the enzyme activity was observed in the first 24 hours, and it was most prominent 48 hours after the administration of aluminum in the mitochondrial fractions when the activity of the enzyme was 31%, 29% and 18.9% of the control value, and after 24 hours in the microsomal fractions when the activity of the enzyme was 43%, 48% and 32% of the control value in the cortex, hippocampus and thalamus, respectively. 96 hours after the administration of aluminum the activity of the enzyme was 63%, 57% and 31% of the value in the control group in mitochondrial, and 100%, 80% and 73% of the control value in microsomal fractions in cortex, hippocampus and thalamus. Plasma levels of aluminum were significantly elevated 24 hours after administration of aluminum. After 48 hours the values were doubled in comparison with the control, 72 hours later plasma concentrations of aluminum were decreased, and after 96 hours they reached the value in the control group. We can conclude that a single oral dose (LD50) of aluminum causes the changes in the brain acetylcholinesterase activity. The changes are still present when the aluminum concentration in plasma is normalized.

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Acetylcholinesterase provides deeper insights into Alzheimer's disease

Cited by 23 publications

References 69 publications

Stable Complexes Involving Acetylcholinesterase and Amyloid-β Peptide Change the Biochemical Properties of the Enzyme and Increase the Neurotoxicity of Alzheimer’s Fibrils

Stable Complexes Involving Acetylcholinesterase and Amyloid-β Peptide Change the Biochemical Properties of the Enzyme and Increase the Neurotoxicity of Alzheimer’s Fibrils

Toxic effects of acetylcholinesterase on neuronal and glial-like cells in vitro

Acetylcholinesterase Activity in the Mongolian Gerbil Brain after Acute Poisoning with Aluminum

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