title: C1q-calreticulin induced oxidative neurotoxicity: relevance for the neuropathogenesis of Alzheimer's disease.
abstract: Alzheimer's disease (AD) remains one of the most challenging brain disorders facing modern medicine. Neuronal loss underlies the pathogenesis of AD and can occur, in part, by oxidative stress, by beta-amyloid peptide (Abeta), and by excitotoxins. The complement cascade, especially C1q, may affect reactive oxygen species (ROS) and mediate neuronal injury during AD. We demonstrate that incubation of neurons with purified C1q results in increased ROS, which can be partially blocked by low concentrations of Abeta. C1q-binding sites on neurons were demonstrated by 125I-C1q-binding and immunofluorescence tests performed on primary neurons. The blocking of neuronal calreticulin by its antibody abrogated ROS by C1q. We suggest that the C1q may be an important factor contributing to neuronal oxidative stress and neuronal demise during AD.
authors.affiliation: Center for Neurovirology and Neurodegenerative Disorders, Department of Pathology and Microbiology, University of Nebraska Medical Center, 985215 Nebraska Medical Center, Omaha, NE 68198-5215, USA.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Luo
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Weber
authors.forename: Jialin
authors.initials: J
authors.lastname: Zheng
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: Tsuneya
authors.initials: T
authors.lastname: Ikezu
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D037282:Calreticulin / Q000032:analysis / Q000502:physiology*; D002478:Cells, Cultured; D015922:Complement C1q / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005455:Fluorescent Antibody Technique; D009474:Neurons / Q000187:drug effects*; D018384:Oxidative Stress; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D037282:Calreticulin; D017382:Reactive Oxygen Species; D013481:Superoxides; D015922:Complement C1q