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Neurotrophin secretion: current facts and future prospects
Volkmar Lessmann1, Kurt Gottmann, Marzia Malcangio
1Department of Physiology and Pathophysiology, Johannes Gutenberg-University Mainz, Duesbergweg 6, Mainz 55128, Germany. lessmann@uni-mainz.de
Progress in Neurobiology
|June 6, 2003
Summary
Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), regulate synaptic function. This review details activity-dependent secretion of BDNF, crucial for synaptic plasticity and neuronal communication.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), were initially recognized for their roles in neuronal survival.
- Emerging evidence highlights their involvement in regulating synaptic transmission and synaptogenesis within the central nervous system (CNS), with a particular focus on BDNF.
Purpose of the Study:
- To review current knowledge on neurotrophin secretion, emphasizing activity-dependent synaptic release of BDNF.
- To address critical questions regarding the sites and activity patterns that trigger neurotrophin release.
- To critically examine the formation and trafficking of neurotrophin precursor molecules.
Main Methods:
- Literature review of existing research on neurotrophin secretion.
- Analysis of data concerning the processing, formation, and trafficking of neurotrophin precursor molecules.
- Comparison of neurotrophin secretion characteristics with those of other neuropeptides.
Main Results:
- Neurotrophin secretion sites (axonal vs. dendritic, synaptic vs. extrasynaptic) and release-triggering activity patterns are key areas requiring detailed understanding.
- The modality and site of neurotrophin secretion are determined by the processing and targeting of their precursor molecules.
- Neurotrophin secretion shares similarities, though not identity, with the secretion mechanisms of other neuropeptides.
Conclusions:
- Understanding neurotrophin secretion is essential for elucidating their role in synaptic function.
- Activity-dependent synaptic release of BDNF is a critical mechanism for synaptic plasticity, such as long-term potentiation (LTP) in the hippocampus.
- Reconciling the proposed role of BDNF as an intercellular synaptic messenger in LTP with its secretion features is an ongoing area of research.