Interaction of survival and death signaling in basal forebrain neurons: Role of neurotrophins and proneurotrophins (J Neurosci, 2006, 26:7756-7766)

報告日期: 2007/11/30
報告時間: 15:10/16:00
報告學生: 鄧志娟
講評老師: 郭余民

Interaction of Survival and Death Signaling in Basal

Forebrain Neurons: Roles of Neurotrophins

And Proneurontrophins


The Journal of Neuroscience, 2006. 26:7756-7766


Speaker: 鄧志娟

Commentator: 郭余民 教授

Time: 2007/11/30, 15:10-16:00

Place: Room 602


    Neurotrophins include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and NT4. They have been shown to influence multiple aspects of neuronal function, such as facilitation of survival and differentiation, regulation of synaptic activity, and induction of apoptosis. Cell survival and death controlled by neurotrophins are mediated by two transmembrane glycoprotein, Trk receptor kinase and p75 neurotrophin receptor.(2) These receptors are often present on the same cell, allowing coordination and modulation of the responses of neurons to neurotrophins. The function of neurotrophin receptors vary markedly, ranging from sculpting and developing nervous system to regulating the survival and regeneration of injured neurons. Pro-NGF is an unprocessed precursor of neurotrophin NGF, which becomes abundant after spinal cord injury and cortical neuron lesions. Pro-NGF has been suggested to be a death-inducing ligand for p75 but not Trk. However, it remains unclear whether pro-NGF is a true pathophysiological ligand that is secreted, binds p75, and activates cell death in vivo,.(1) This study shows that pro-neurotrophins were produced in the brain under pathological conditions and elicited apoptosis of basal forebrain neurons even when Trk receptors are activated. Pro-neurotrophins interfered with the pro-survival signaling downstream of Trk activation by blocking PI3K/Akt and/or Mek/Erk phospholarylation and leading apoptosis. Thus, neurotrophin actions in the brain influence neuronal survival and death, according to which receptor and signaling pathways are activated. This suggests the potential use of neurotrophins as therapeutic agents in neuronal disease.       



1.         Harrington, A. W., B. Leiner, C. Blechschmitt, J. C. Arevalo, R. Lee, K. Morl, M. Meyer, B. L. Hempstead, S. O. Yoon, and K. M. Giehl. 2004. Secreted proNGF is a pathophysiological death-inducing ligand after adult CNS injury. Proc Natl Acad Sci U S A 101:6226-30.

2.         Kaplan, D. R., and R. M. Stephens. 1994. Neurotrophin signal transduction by the Trk receptor. J Neurobiol 25:1404-17.