Brain-Derived Neurotrophic Factor Inhibits Phenylalanine-Induced Neuronal Apoptosis by Preventing RhoA Pathway Activation |
| |
Authors: | Yongjun Zhang Jing Zhao Jing Wang Xianting Jiao |
| |
Institution: | (1) XinHua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665#, 200092 Shanghai, China |
| |
Abstract: | Phenylketonuria (PKU) is neuropathologically characterized by neuronal cell loss, white matter abnormalities, dendritic simplification,
and synaptic density reduction. The neuropathological effect may be due to the ‘toxicity’ of the high concentration of phenylalanine,
while little is known about the related treatments to block this effect. In this study, we reported that brain-derived growth
factor (BDNF) protected neurons from phenylalanine-induced apoptosis and inhibition of Trk receptor by K252a or downregulation
of TrkB abrogated the effect of BDNF. We further demonstrated that phenylalanine-induced RhoA activation and myosin light
chain phosphorylation were inhibited by pretreatment with BDNF, while phenylalanine activates the mitochondria-mediated apoptosis
through the RhoA/Rho-associated kinase pathway. Thus our studies indicate that the protective effect of BDNF against phenylalanine-induced
neuronal apoptosis is probably mediated by suppression of RhoA signaling pathway via TrkB receptor. Taken together, these
findings suggest a potential neuroprotective action of BDNF in prevention and treatment of PKU brain injury. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|