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Effects of proNGF on Neuronal Viability, Neurite Growth and Amyloid-beta Metabolism

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An Erratum to this article was published on 03 September 2011

Abstract

Alzheimer’s disease (AD) is characterized pathologically by the deposition of amyloid-β peptides (Aβ), neurofibrillary tangles, distinctive neuronal loss and neurite dystrophy. Nerve growth factor (NGF) has been suggested to be involved in the pathogenesis of AD, however, the role of its precursor (proNGF) in AD remains unknown. In this study, we investigated the effect of proNGF on neuron death, neurite growth and Aβ production, in vitro and in vivo. We found that proNGF promotes the death of different cell lines and primary neurons in culture, likely dependent on the expression of p75NTR. We for the first time found that proNGF has an opposite role in neurite growth to that of mature NGF, retarding neurite growth in both cell lines and primary neurons. proNGF is localized to the Aβ plaques in AD mice brain, however, it had no significant effect on Aβ production in vitro and in vivo. Our findings suggest that proNGF is an important factor involving AD pathogenesis.

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Acknowledgements

We wish to thank Ms. Jin-Xian Mi, Sheona Page in Flinders University for preparation of sheep anti-proNGF antibody, Dr. Moses Chao in New York University for providing rabbit antibody directed against p75 neurotrophin receptor. This project is supported by NHMRC grant (No. 480422, X. F. Zhou & Y. J. Wang). Y. J. Wang is supported by IPRS at Flinders University.

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Correspondence to Xin-Fu Zhou.

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Yan-Jiang Wang, Deborah Valadares and Ying Sun have contributed equally to this work.

An erratum to this article is available at http://dx.doi.org/10.1007/s12640-011-9270-y.

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Wang, YJ., Valadares, D., Sun, Y. et al. Effects of proNGF on Neuronal Viability, Neurite Growth and Amyloid-beta Metabolism. Neurotox Res 17, 257–267 (2010). https://doi.org/10.1007/s12640-009-9098-x

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