Release of acetylcholinesterase (AChE) from beta-amyloid plaques assemblies improves the spatial memory impairments in APP-transgenic mice.
The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid-beta-peptide (Abeta). Amyloid deposits contain "chaperone molecules" which play critical roles in amyloid formation and toxicity. In the present work, we test an analog of hyperforin (IDN 5706) which releases the AChE from both the Abeta fibrils and the AChE-Abeta burdens in transgenic mice. Hyperforin is an acylphloroglucinol compound isolated from Hypericum perforatum (St. John's Wort), which is able to prevent the Abeta-induced spatial memory impairments and Abeta neurotoxicity. Altogether this gathered evidence indicates the important role of AChE in the neurotoxicity of Abeta plaques and finding new compounds which decrease the AChE-Abeta interaction may be a putative therapeutic agent to fight the disease.
Dinamarca
Margarita C
MC
Centro de Regulación Celular y Patología Joaquín V. Luco, Centro de Envejecimiento y Regeneración (CARE), MIFAB, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile.
Arrázola
Macarena
M
Toledo
Enrique
E
Cerpa
Waldo F
WF
Hancke
Juan
J
Inestrosa
Nibaldo C
NC
D000110:Acetylcholinesterase / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology*; D000818:Animals; D007150:Immunohistochemistry; D008569:Memory Disorders / Q000201:enzymology*; D051379:Mice; D008822:Mice, Transgenic
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000110:Acetylcholinesterase