%0 Journal Article
%T Receptor Tyrosine Kinases: Molecular Switches Regulating CNS Axon Regeneration
%A Vasanthy Vigneswara
%A Sarina Kundi
%A Zubair Ahmed
%J Journal of Signal Transduction
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/361721
%X The poor or lack of injured adult central nervous system (CNS) axon regeneration results in devastating consequences and poor functional recovery. The interplay between the intrinsic and extrinsic factors contributes to robust inhibition of axon regeneration of injured CNS neurons. The insufficient or lack of trophic support for injured neurons is considered as one of the major obstacles contributing to their failure to survive and regrow their axons after injury. In the CNS, many of the signalling pathways associated with neuronal survival and axon regeneration are regulated by several classes of receptor tyrosine kinases (RTK) that respond to a variety of ligands. This paper highlights and summarises the most relevant recent findings pertinent to different classes of the RTK family of molecules, with a particular focus on elucidating their role in CNS axon regeneration. 1. Introduction In the mammalian central nervous system (CNS), the failure of spontaneous regeneration of injured axons leads to devastating consequences and poor functional recovery. Severe injuries to CNS axons not only damage plasticity of synapses but also provoke complex degenerative cascades, leading to glial and neuronal apoptosis. The vast majority of injured CNS neurons progressively fails to regenerate beyond the lesion site to reestablish functional synaptic transmission and only a small number of axons show compensatory sprouting, resulting in poor functional recovery [1¨C5]. Lack or insufficient trophic support is one of the major determinants attributed to the failure of adult CNS axon regeneration. Growth factors that act both on neurons and glia, mediate a variety of physiological functions from early embryonic to the adult state, including synaptic plasticity, cell survival, and death in the CNS [6¨C10]. Hence, trophic factors and their corresponding receptor-mediated signalling pathways involved in neuronal survival and axon regeneration have been subjected to considerable attention. Many of these studies have been aimed at developing potential therapeutic interventions for the treatment of peripheral nervous system (PNS) and CNS injuries and certain neurodegenerative disorders like Parkinson¡¯s and Alzheimer¡¯s diseases. 2. Mechanisms behind the Failure of CNS Axon Regeneration In general, functional axon regeneration is a multifactorial process; a myriad of molecules and a combination of signalling pathways are often involved. Two important prerequisites are essential for successful regeneration. Firstly, the injured neurons must be competent to survive after injury,
%U http://www.hindawi.com/journals/jst/2012/361721/