. Acetylcholinesterase induces neuronal cell loss, astrocyte hypertrophy and behavioral deficits in mammalian hippocampus. J Neurochem. 2003 Oct;87(1):195-204. PubMed.

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  1. Concerning AChE as a fibril former, it is interesting to recall that AChE by its peripheral site was able to accelerate amyloid fibril formation, in a reaction that was blocked by a specific monoclonal antibody (Reyes et al., 1997). Later on, it was shown that a 4KDa hydrophobic peptide of AChE was by itself able to perform the same job as the entire enzyme (De Ferrari et al., 2001). We have been able to confirm some but not all of Cottighman´s studies. In particular, we have not been able to see the thioflavin-T binding to the C-terminal domain. Interestingly enough, despite all these years, AChE remains an issue in Alzheimer's disease.

    References:

    . A monoclonal antibody against acetylcholinesterase inhibits the formation of amyloid fibrils induced by the enzyme. Biochem Biophys Res Commun. 1997 Mar 27;232(3):652-5. PubMed.

    . A structural motif of acetylcholinesterase that promotes amyloid beta-peptide fibril formation. Biochemistry. 2001 Sep 4;40(35):10447-57. PubMed.

    View all comments by Marcela Colombres
  2. I would like to point out that several years ago, we found that AChE was able to stimulate the aggregation of the amyloid-β peptide, and later on, we characterized the amyloid-β peptide AChE complexes. Such complexes were more toxic than the amyloid-β fibril itself, indicating that AChE is not only a companion of amyloid-β peptide in amyloid plaque, but a real player in the neurotoxicity of amyloid-β peptide.

    References:

    . Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer's fibrils: possible role of the peripheral site of the enzyme. Neuron. 1996 Apr;16(4):881-91. PubMed.

    . Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils. J Mol Biol. 1997 Sep 26;272(3):348-61. PubMed.

    . Stable complexes involving acetylcholinesterase and amyloid-beta peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer's fibrils. J Neurosci. 1998 May 1;18(9):3213-23. PubMed.

    View all comments by Alejandra Alvarez

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  1. Acetylcholinesterase—Enzyme or Fibril Former?