A protease activity associated with acetylcholinesterase releases the membrane-bound form of the amyloid protein precursor of Alzheimer's disease
- 1 November 1991
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 30 (44), 10795-10799
- https://doi.org/10.1021/bi00108a027
Abstract
Amyloid deposits in the brains of patients with Alzheimer's disease (AD) contain a protein (beta A4) which is abnormally cleaved from a larger transmembrane precursor protein (APP). APP is believed to be normally released from membranes by the action of a protease referred to as APP secretase. Amyloid deposits have also been shown to contain the enzyme acetylcholinesterase (AChE). In this study, a protease activity associated with AChE was found to possess APP secretase activity, stimulating the release of a soluble 100K form of APP from HeLa cells transfected with an APP cDNA. The AChE-associated protease was strongly and specifically inhibited by soluble APP (10 nM) isolated from human brain. The AChE-associated protease cleaved a synthetic beta A4 peptide at the predicted cleavage site. As AChE is decreased in AD, a deficiency of its associated protease might explain why APP is abnormally processed in AD.Keywords
This publication has 32 references indexed in Scilit:
- Electron microscopic localization of cholinesterase activity in Alzheimer brain tissueBrain Research, 1991
- Cleavage of Amyloid β Peptide During Constitutive Processing of Its PrecursorScience, 1990
- Distribution of the molecular forms of acetylcholinesterase in human brain: Alterations in dementia of the Alzheimer typeAnnals of Neurology, 1986
- Molecular Forms of Acetylcholinesterase from Human Caudate Nucleus: Comparison of Salt‐Soluble and Detergent‐Soluble Tetrameric Enzyme SpeciesJournal of Neurochemistry, 1985
- Peptide synthesis. Part 2. Procedures for solid-phase synthesis using Nα-fluorenylmethoxycarbonylamino-acids on polyamide supports. Synthesis of substance P and of acyl carrier protein 65–74 decapeptideJournal of the Chemical Society, Perkin Transactions 1, 1981
- Neurotransmitter-related enzymes in senile dementia of the alzheimer typeBrain Research, 1979
- SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASEThe Lancet, 1976
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976
- ENZYME HISTOCHEMICAL STUDIES OF SENILE PLAQUESJournal of Neuropathology and Experimental Neurology, 1965
- A new and rapid colorimetric determination of acetylcholinesterase activityBiochemical Pharmacology, 1961