title: Nogo-66 receptor activation inhibits neurite outgrowth and increases             β-amyloid protein secretion of cortical neurons.
abstract: A Nogo-A to Nogo-66 receptor (NgR) pathway is well known to contribute to the inhibition of the neurite regeneration of adult central nervous system neurons after traumatic injuries. Recent evidence suggests that Nogo-A and NgR are involved in the pathology of Alzheimer's disease (AD), as evidenced by the fact that Nogo-A is overexpressed by hippocampal neurons in patients with AD and is associated with β-amyloid protein (Aβ) deposits in senile plaques. In the present experiments, we investigated the potential role of Nogo-A in both neurite outgrowth and Aβ generation in cortical neurons. Our results showed that activation of NgR not only inhibited neurite outgrowth in cortical neurons by activating the rho-associated coiled coil-containing protein kinase (ROCK) and protein kinase C, but also promoted their Aβ secretion, which was at least in part activated by ROCK. These findings suggest that the overexpression of Nogo-A and the activation of NgR inhibit neurite outgrowth and alter neuronal metabolism, resulting in overproduction and/or release of Aβ, which in turn may trigger the onset and development of AD. Inhibition of ROCK can promote neurite outgrowth and reduce Aβ production of cortical neuron, which suggests that ROCK appears to be a good target for AD therapy.
authors.affiliation: Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.forename: Lian-Feng
authors.initials: LF
authors.lastname: Lin
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.forename: Qin
authors.initials: Q
authors.lastname: Gao
authors.forename: Huan-Min
authors.initials: HM
authors.lastname: Luo
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D058851:GPI-Linked Proteins / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism* / Q000494:pharmacology; D016501:Neurites / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D000070816:Nogo Receptor 1; D010446:Peptide Fragments / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; C457761:NEPI-40 protein, rat; D000070816:Nogo Receptor 1; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C486581:Rtn4r protein, rat; D054460:rho-Associated Kinases; D011493:Protein Kinase C