**4. UPS in neuronal signalling**

In the nervous system, UPS is present in neurons, glia and synapses and regulates numerous functions including neuronal signalling, synapse assembly, maintenance, and function [Mengual et al., 1996]. Recent work utilizing the powerful genetic tools in *C. elegans* and *Drosophila* as well as synaptic assays in mammalian neuronal culture systems has unravelled the critical role of UPS in neuronal signaling. Active E3 ligases are identified at the synapse which participates in synaptic plasticity [Myat et al., 2002]. Moreover, localization of many E3 ligases in nucleus and synapse suggests the interplay between UPS regulation of transcriptional programs that function in synaptic modulation and local synaptic regulation of protein degradation.

UPS regulates synaptic functions by controlling levels of pre-synaptic proteins [Speese et al., 2003]. At the post-synaptic levels, the UPS regulates the surface expression and internalization of NMDA- and AMPA-glutamate receptors [Moriyoshi et al., 2004]. It has been implicated that mechanical allodynia and hyperalgesia can be prevented with NMDAreceptor antagonists [Laughlin et al., 1997**]**. During pathological pain UPS regulates neuronal signalling by controlling levels of synaptic proteins [Ossipov et al, 2007]. Much future work is needed to identify exact role of UPS in acute and chronic pain conditions.
