Author: Dominique Bagnard,

Source: Current Pharmaceutical Design, Volume 13, Number 24, August 2007 , pp. 2469-2469(1)

Publisher: Bentham Science Publishers

Abstract:

While thought to be irremediable for a long time, nervous system lesions are may be close to be treatable. This hope comes from the fantastic progress in identifying the molecular nature of neurite growth inhibitory factors accumulated in the lesion sites and contributing to the lack of nerve regeneration. A wide range of secreted or membrane bound factors have been shown to trigger growth inhibitory pathways. In parallel to the elucidation of the molecular mechanisms involved, multiple approaches devoted to antagonize inhibitory factors have been designed worldwide. In this special issue we decided to present current advance of some of the famous strategies such as the anti-Nogo strategy [1] or the use of condhroitinases [2] together with related developments such as the interference of the Rho/ROCK pathway [3] or the application of the new concept of DNA vaccine to growth inhibitory factors [4]. Guidance molecules which normally contribute to brain wiring during development are now entering the dance of the factors impeding nerve regeneration. This potential reservoir of new therapeutic targets is discussed here for the eph/ephrins family [5]. Thus, there is no doubt that our knowledge of growth inhibitory factors has never been so good to tempt therapeutic interventions but what about the in vivo situation? Do we have appropriate technological tools to reach the lesion site and inactivate the factors in the right place? As presented in the review by Ellis-Behnke and colleagues [6], the use of nanotechnology may have an outstanding impact on our capacity to interfere with inhibitory growth factors. Hence, we also included a review by the group of Z.C. Xiao [7] reminding that these factors are not solely expressed in case of lesion but also have physiological roles, often not fully understood. As discussed in this paper, a particular effort must be maintained to better understand the complex biological functions of all of these molecules. This should be at some point considered as an absolute prerequisite to ensure the design of therapeutic without high risk of severe adverse effects.

References

[1] Walmsley AR, Mir AK. Targeting the Nogo-A Signalling Pathway to Promote Recovery Following Acute CNS Injury. Curr Pharm Des 2007; 13(24): 2470-2484.

[2] Del Rio JA, Soriano E. Overcoming Chondroitin Sulphate Proteoglycan Inhibition of Axon Growth in the Injured Brain: Lessons from Chondroitinase ABC. Curr Pharm Des 2007; 13(24): 2485-2492.

[3] Kubo T, Hata K, Yamaguchi A, Yamashita T. Rho-ROCK Inhibitors as Emerging Strategies to Promote Nerve Regeneration. Curr Pharm Des 2007; 13(24): 2493-2499.

[4] Nie D-y, Xu G, Ahmed S, Xiao Z-c. DNA Vaccine and the CNS Axonal Regeneration. Curr Pharm Des 2007; 13(24): 2500-2506.

[5] Du J, Fu C, Sretavan DW. Eph/ephrin Signaling as A Potential Therapeutic Target After Central Nervous System Injury. Curr Pharm Des 2007; 13(24): 2507-2518.

[6] Ellis-Behnke RG, Teather LA, Schneider GE, So K-F.Using Nanotechnology to Design Potential Therapies for CNS Regeneration. Curr Pharm Des 2007; 13(24): 2519-2528.

[7] Ma Q-H, Yang W-L, Nie D-Y, Dawe GS, Xiao Z-C. Physiological Roles of Neurite Outgrowth Inhibitors at Myelinated Axons in the Central Nervous System-Implications for the Therapeutic Neutralization of Neurite Outgrowth Inhibitors. Curr Pharm Des 2007; 13(24): 2529-2537.

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161207781368666

Affiliations: 1: INSERM U575 Physiopathologie du Systeme Nerveux Centre de Neurochimie 5 rue blaise Pascal 67084 Strasbourg France.

Publication date: 2007-08-01

More about this publication?

• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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