Valproic acid enhances microglial phagocytosis of amyloid-beta(1-42).
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder manifested by memory loss, confusion and changes in mood. A principal pathology of this debilitating disorder is extracellular deposits of amyloid-beta (Abeta) protein. The "amyloid hypothesis" postulates that a build-up of Abeta protein is responsible for neuronal loss and the ensuing symptoms of AD. One possible mechanism of Abeta clearance, and hence AD therapy, is phagocytosis of Abeta protein by microglial cells. Microglia are the brain's resident immune cells and phagocytosis is one of their innate functions. We are interested in identifying molecules that augment microglial-mediated phagocytosis of Abeta protein. We used the rodent BV-2 microglial cell line which readily phagocytose fluorescent latex beads and synthetic Abeta(1-42) peptide. BV-2 cells treated with the neuroactive drug valproic acid (VPA) showed greatly enhanced phagocytic activity for both latex beads and Abeta. VPA also reduced microglial viability by inducing apoptosis, as previously reported. The relevance of these in vitro results to the treatment of AD is unclear but further investigation into the effects of VPA on the clearance of Abeta through enhanced microglial phagocytosis is warranted.
Smith
A M
AM
Department of Pharmacology, Faculty of Medical and Health Sciences and the National Research Centre for Growth and Development, The University of Auckland, Auckland, New Zealand.
Gibbons
H M
HM
Dragunow
M
M
D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002460:Cell Line / Q000187:drug effects / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D008863:Microspheres; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects*; D013268:Stimulation, Chemical; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D014635:Valproic Acid