Neurogenesis and Neuroprotection in Huntington Disease

Adult neurogenesis is attributed to the activity of progenitor cells whose progeny progressively mature to functional neurons under genetic and epigenetic influence. Due to the significant role of FGF6 (fibroblast growth factor 6), in the skeletal growth, and maintenance of progenitor cells in skeletal muscle, and the role of HDAC inhibitors (histone deacetylase inhibitors) in promoting neurogenesis, and increasing of neuronal proliferation, a combination of FGF6 with HDAC inhibitor CHDI-3 is investigated as a potential treatment to lessen neuronal loss in HD, by enhancing neurogenesis. Fascinatingly, FGF6 and HDAC inhibitor CHDI-3 treatment was found to be significantly neuroprotective in the expended huntingtin cell linesHdh111Q/111Q model 24hours after treatment during serum withdrawal. Results also show that FGF6 combined with HDAC inhibitor CHDI-3 was found to activate both pERK1/2and BDNF pathways in the expended huntingtin cell linesHdh111Q/111Q model 1 hour after treatment. In addition, results from Morris water maze indicate that neurogenesis inhibition negatively regulates the learning and spatial memory, and that neurogenesis occurs more in the young age, and decreases in the old age. Because pERK1/2, and BDNF pathways activation have been implicated in neurogenesis, synaptic plasticity, learning, and memory and cell survival, we can conclude that FGF6 and HDAC inhibitors combined can be utilized for future therapeutic treatment to improve learning and memory for HD patients due to its enhancement of neurogenesis.