Chapter Five - Stimulating Neurotrophin Receptors in the Treatment of Neurodegenerative Disorders

• Autores: Gunnar Nordvall, Pontus Forsell
• Localización: Annual reports in medicinal chemistry, ISSN 0065-7743, Vol 49, 2014, págs. 59-73
• Idioma: inglés
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• Resumen

  • Abstract Neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease are currently lacking disease-modifying treatments. A substantial body of evidence links increases in neurotrophin (NT) signaling in neurodegenerative disorders with biological mechanisms that could have a positive effect on disease outcome. NTs like NGF and BDNF signal through Trk receptors. This signaling is of high importance to support neuronal survival, differentiation, neurogenesis, and synaptic plasticity. The poor pharmacokinetics of NTs makes them unsuitable as drugs. In addition, the NTs have pleiotropic effects that may give side effects. Therefore, the identification of small molecules that promote NT signaling is of increasing interest. Such small-molecule activators of NT signaling will support neuronal survival in the CNS, and thus they could possibly function as disease modifiers. Herein, we review the current status of small-molecule compounds that are able to activate NT receptors.