TY - JOUR
T1 - C1q-calreticulin induced oxidative neurotoxicity
T2 - Relevance for the neuropathogenesis of Alzheimer's disease
AU - Luo, Xiaoguang
AU - Weber, Gregory A.
AU - Zheng, Jialin
AU - Gendelman, Howard E.
AU - Ikezu, Tsuneya
N1 - Funding Information:
The authors thank Hui Peng, David Erichsen, Garrett Pohlman, James Buescher, and Sam Sanderson for research support and lively scientific exchanges, and Robin Taylor for providing editorial assistance. This work is supported by the Vada Oldfield Alzheimer Research Foundation (T.I.), University of Nebraska Medical Center (UNMC) Start-up Fund (T.I.), the David T. Purtilo Chair of Pathology at UNMC (H.E.G.), and World Health Organization Fellowship (X.L.).
PY - 2003/2
Y1 - 2003/2
N2 - 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 β-amyloid peptide (Aβ), 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 Aβ. 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.
AB - 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 β-amyloid peptide (Aβ), 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 Aβ. 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.
KW - C1q
KW - Calreticulin
KW - Neurons
KW - Reactive oxygen species
KW - β-Amyloid peptide
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U2 - 10.1016/S0165-5728(02)00444-7
DO - 10.1016/S0165-5728(02)00444-7
M3 - Article
C2 - 12576225
AN - SCOPUS:0037308834
SN - 0165-5728
VL - 135
SP - 62
EP - 71
JO - Journal of neuroimmunology
JF - Journal of neuroimmunology
IS - 1-2
ER -