Dysregulation of Ca2+ homeostasis in Alzheimer's disease: role in acetylcholinesterase production and AMPA receptor internalization.
Amyloid-β (Aβ)-induced Ca(2+) influx into neurons has been well described since it was first reported almost 20 years ago. Ca(2+) influx can disrupt mechanisms of long-term potentiation and long-term depression and increase neuronal susceptibility to excitotoxicity. Our studies show that Aβ also causes an increase in acetylcholinesterase (AChE) levels and induces AMPA receptor internalization through Ca(2+)-dependent mechanisms. As Aβ-induced Ca(2+) entry may increase neuronal excitability, the increase in AChE and the downregulation of cell surface AMPA receptors may be part of a homeostatic mechanism which maintains normal levels of cholinergic and glutamatergic signaling.
Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tas, Australia. d.h.small@menzies.utas.edu.au
David H
DH
Small
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects
D016229:Amyloid beta-Peptides; D018091:Receptors, AMPA; D000110:Acetylcholinesterase; D002118:Calcium