Effects of proNGF on neuronal viability, neurite growth and amyloid-beta metabolism

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 p75 ^NTR. 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.