Relationship between beta-AP peptide aggregation and microglial activation.
We compared the relationship between the state of aggregation of two peptides (beta-AP 25-35 and beta-AP 1-42) and microglial activation. After 7 days at 37 degrees C beta-AP 25-35 was in an amorphous state and did not activate microglial cells. In the same conditions, aggregated beta-AP 1-42 activated these cells and caused changes in microglial ramification, increasing the proliferation index and inducing tumor necrosis factor alpha (TNF alpha) release. Neither peptide induced a release of nitric oxide (NO). As the toxicity of beta-AP peptides in cell culture is associated with the formation of amyloid fibrils, we also examined the toxicity of both peptides in microglial cell cultures and in PC 12 cell cultures. The results suggest that the two beta-AP fragments studied have similar neurotoxic effects but different pro-inflammatory activities.
Casal
Carme
C
Department of Pharmacology and Toxicology, Institut d'Investigacions Biomèdiques de Barcelona, CSIC, IDIBAPS, C/Rossello 161, 6a planta, E-08036 Barcelona, Spain.
Serratosa
Joan
J
Tusell
Josep M
JM
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D004660:Encephalitis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005911:Gliosis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D009569:Nitric Oxide; D019001:Nitric Oxide Synthase