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Neurotoxicity of acetylcholinesterase amyloid β‐peptide aggregates is dependent on the type of Aβ peptide and the AChE concentration present in the complexes
Author(s) -
Muñoz Francisco J.,
Inestrosa Nibaldo C.
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00468-8
Subject(s) - acetylcholinesterase , neurotoxicity , aché , peptide , senile plaques , chemistry , neurodegeneration , fibril , amyloid (mycology) , biochemistry , biophysics , enzyme , alzheimer's disease , medicine , toxicity , biology , inorganic chemistry , disease , organic chemistry
Alzheimer's disease (AD) is a neurodegenerative disorder whose hallmark is the presence of senile plaques and neurofibrillary tangles. Senile plaques are mainly composed of amyloid β‐peptide (Aβ) fibrils and several proteins including acetylcholinesterase (AChE). AChE has been previously shown to stimulate the aggregation of Aβ 1–40 into amyloid fibrils. In the present work, the neurotoxicity of different amyloid aggregates formed in the absence or presence of AChE was evaluated in rat pheochromocytoma PC12 cells. Stable AChE‐Aβ complexes were found to be more toxic than those formed without the enzyme, for Aβ 1–40 and Aβ 1–42 , but not for amyloid fibrils formed with Aβ Val18→Ala , a synthetic variant of the Aβ 1–40 peptide. Of all the AChE‐Aβ complexes tested the one containing the Aβ 1–40 peptide was the most toxic. When increasing concentrations of AChE were used to aggregate the Aβ 1–40 peptide, the neurotoxicity of the complexes increased as a function of the amount of enzyme bound to each complex. Our results show that AChE‐Aβ 1–40 aggregates are more toxic than those of AChE‐Aβ 1–42 and that the neurotoxicity depends on the amount of AChE bound to the complexes, suggesting that AChE may play a key role in the neurodegeneration observed in Alzheimer brain.