´╗┐Indeed, CDK5/p35 phosphorylates at Ser-396 and Ser-404 residues in response to A25C35 [103]. Aberrant CDK5 activity is induced by the conversion of p35 to p25 by calpain, a Ca2+-dependent cysteine protease. the treatment of neuropathic pain, and the anti-epileptic conantokin-G, isolated from L. Currently undergoing a more advanced evaluation, Hwass in Bruguire) for neuropathic pain treatment, and contulakin-G (from [12] focused their attention on marine drugs affecting ion channels, and Al-Sabi [13] reviewed data about marine toxins that target voltage-gated sodium channels. Kochanowska-Karamyan and Hamann [14] covered the role of marine indole alkaloids as potential new antidepressant and anti-anxiety drug leads. Bharate [15] and Skropeta [16] gathered information concerning sponge drugs with RO4987655 protein kinase inhibitory activity. A broader spectrum of enzyme inhibited by marine drugs was covered by Nakao and Fusetani [17]. Senthilkumar and Kim [18] compiled information concerning marine invertebrate natural drugs for inflammatory and chronic diseases, including AD. Finally, information regarding preclinical and clinical candidates in the field of neurology was published by Martnez [19], Twede [10] and Bharate [15]. 2. The Nervous System The nervous system is the network of specialized cells that conduct nerve impulses between parts of the body. The central nervous system (CNS) is responsible for driving and interpreting signals and for supplying excitatory stimuli to the peripheral nervous system (PNS); PNS nerves innervate muscle tissue, conducting sensory and excitatory stimuli to and from the spinal cord [20]. Besides neurons, whose function is to propagate nerve impulses, CNS and PNS also contain another type of cells called glial cells or neuroglia. Neuroglia comprises four types of cells, namely, astrocytes, oligodendrocytes, microglia cells in the CNS and Schwann cells in the PNS. Astrocytes are a very heterogeneous population of cells and they can interfere in axon guidance, synaptic support, control of the bloodCbrain barrier (BBB) and blood flow [21]. These are excitable cells like neurons, but they communicate by spontaneous or evoked cytosolic Ca2+ variations, instead of membrane electrical signals [22]. Oligodendrocytes and Schwann cells are responsible for the production of myelin [21,23]. Microglia cells are the immune cells of the CNS, contributing to CNS homeostasis during development, adulthood and ageing [24]. They protect the brain from damage and infection, by engulfing dead cells and debris. They are also implicated in synaptic remodelling during the development of the nervous system and they are activated in many neurodegenerative diseases [21,23]. In the nervous system, glial cells are more abundant than neurons and have some capacity for cell division. Conversely, neurons RO4987655 have no capacity for mitotic division, but can regenerate portions under certain conditions [20]. 3. Regeneration of the CNS: Drawbacks and Challenges Complete recovery from a CNS injury or neurological disorders has not yet been made possible [25]. This is because an injury is a continuous process, with a primary damage triggering a cascade of deleterious events, such as bloodCbrain barrier disruption, excitotoxicity, inflammation, oedema, ischemia, increase of free radicals and altered cell signalling and gene expression [26,27]. Therefore, a massive death of neuronal and glial cells may occur CXCL5 along with the loss of both the 3D spatial organization and the connectivity of neuronal networks [28]. Although neurite growth inhibitors are present in both CNS and PNS, the capacity for CNS nerves to regenerate is lower than that of peripheral nerves for several reasons. First, because astrocytes become reactive astrocytes, which produce glial scars that constitute a physical barrier to growth and up-regulate several extracellular-matrix-associated inhibitors of regeneration, such as chondroitin sulfate proteoglycans [29]. Second, conversely to a PNS injury, in the case of a CNS injury, BBB and bloodCspine barrier function as constrainers to the recruitment of macrophages from the blood circulation to remove myelin and axonal debris and resident microglia can only give a delayed and slow response [24,30,31]. Moreover, in contrast to PNS, the up-regulation of regeneration-associated proteins (RAGs), which play a positive role in neurite outgrowth and axon regeneration, is relatively modest in the CNS after injury [32,33]. In order to counteract this low regenerating environment after a CNS injury, clinical trials have taken advantage of the recent progress in regenerative medicine, and new approaches for the treatment of CNS injuries have RO4987655 been explored, such as (i).