Alterations of some membrane transport proteins in Alzheimer's disease: role of amyloid beta-peptide.
Alzheimer's disease (AD) is the most common neurodegenerative disease characterized clinically by progressive memory loss and decline in cognitive abilities and characterized pathologically by the presence of two types of abnormal deposits, i.e., senile plaques (SP) and neurofibrillary tangles (NFT), and by extensive synapse and neuronal loss. SP are composed of fibrillar amyloid beta-peptide (Abeta) surrounded by dystrophic neurites. Recent studies suggest two prospective mechanisms for Abeta-associated membrane dysfunction and subsequent neurotoxicity. One suggests that Abeta oligomers can form heterogeneous ion-channels in the cell membrane leading to cellular degeneration, while the second suggests insertion of Abeta oligomers in membrane lipid bilayers could induce the dysfunction of ion-channels or pumps by binding to or inducing oxidative modification of membrane proteins. In this review, we discuss the effects of Abeta on membrane proteins that are involved in cholinergic and glutamatergic pathways, and some ion-channels.
Sultana
Rukhsana
R
Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA.
Butterfield
D Allan
DA
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism / Q000502:physiology; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000502:physiology*; D008954:Models, Biological; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology; D011950:Receptors, Cholinergic / Q000378:metabolism / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism / Q000502:physiology
D016229:Amyloid beta-Peptides; D015220:Calcium Channels; D027342:Excitatory Amino Acid Transporter 2; D026901:Membrane Transport Proteins; D015221:Potassium Channels; D011950:Receptors, Cholinergic; D005973:Glutamine; D000254:Sodium-Potassium-Exchanging ATPase