Conclusions And Future Perspectives

Synaptogenesis is a multistep process that underlies the formation of precise synaptic connections. Because neurotrophins regulate structure and function of both pre- and postsynaptic elements, this class of secreted proteins are attractive candidates as regulators of synaptogenesis. Firstly, neurotrophins regulate axonal and dendritic morphological changes that may aid in establishing initial contact between synaptic partners. Secondly, neurotrophins induce changes in pre- and postsynaptic elements associated with the formation of new synapses, such as maturation of presynaptic release properties and postsynaptic receptor clustering. Finally, neurotrophins regulate the stabilization and/or elimination of newly formed synapses to form appropriate networks. Taken together, neurotrophins critically regulate several key steps in synaptogenesis (Figure 12.3).

However, there are many outstanding issues and problems. The underlying signaling mechanisms important for the regulation of synapse formation by neurotrophins remain to be elucidated. In addition, p75NTR signaling, highlighted in many recent studies of neurite growth, has not been rigorously examined in synaptogenesis. Multidisciplinary approaches such as in vivo imaging and electrophysiological recording, together with the use of genetically engineered animals, may help us answer these unresolved questions and issues.

Recent breakthroughs in stem cell technology have provided an optimistic view that this technology may be applied in the near future. However, this form of therapy would not be practical if newly generated neurons cannot make appropriate functional synapses. Neurotrophins may conceivably be used to promote synapse formation in both pre-existing and newly generated neurons.

Therefore, it is imperative to understand the diverse mechanisms utilized by neurotrophins to regulate synaptogenesis. This is important not only for our understanding of proper nervous system development but may also aid in the development of neurotrophin-based treatments that will facilitate the regeneration of neurons in the face of neurodegenerative diseases and injury.

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