CYP inhibitor Neurogenesis arises from brain progenitor cells

f CNS diseases, suggesting that neurogenesis is functionally important to recovery. Neurogenesis arises from brain progenitor cells, rather than from differentiated adult neurons. Therapies directed CYP inhibitor at any component inhibiting the cell cycle must be as specific as possible considering cell cycle re entry contributes to both the death of mature neurons and the genesis of neuroprogenitor cells in adult brain. Therefore, any therapeutics that prevent neuronal death by blocking mitogenic signaling may have limited benefit because they may also prevent neurogenesis. This may provide at least a partial explanation for the questionable efficacy of some currently approved drugs, such as the NMDA receptor modulator Memantine, in the clinical treatment of AD, since NMDA receptor activation has been shown to enhance progenitor cell proliferation and lead to increased neurogenesis.
This is consistent with the clinical reports that cognitive dysfunction arises when cell cycle inhibition strategies are used in cancer therapeutics. This cognitive dysfunction may also be explained by the fact that current cell cycle inhibition strategies are not cell specific and also block the proliferation of important brain progenitor cells, thus impairing adult brain neurogenesis. Linezolid Thus, it appears that cell cycle inhibition strategies could help protect neurons and improve disease and injury outcomes, as long as they do not interfere with the growth of other important cells in the brain.
If drugs that block the cell cycle are used to prevent neuronal death in CNS diseases, it is likely that compounds would need to directly block neuronal cell cycle re entry and yet not affect the ongoing process of neurogenesis. This will only be possible if the signaling mechanisms are different in adult progenitor cells that divide in the adult brain, versus adult neurons that re enter the cell cycle. Liu et al. Page 7 Neurobiol Dis. Author manuscript, available in PMC 2011 March 1. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript Conclusions Cell cycle inhibition protects mature neurons from death. However, it is likely that to truly protect neurons, the best strategy may be to ensure they do not leave the G0 phase at all, since the mere entrance into the initial cell cycle may lead to unavoidable cell death.
Moreover, future studies aimed at understanding the respective cell cycle pathways of mature neurons and neuronal progenitors are probably necessary before choosing the best drug targets for treating CNS diseases. Acknowledgments This study was supported by NIH grant NS054652. We thank Mr. James C. Hathaway for helpful discussion and editing of the manuscript. References Abdipranoto A, Wu S, Stayte S, Vissel B. The role of neurogenesis in neurodegenerative diseases and its implications for therapeutic development. CNS Neurol Disord Drug Targets 2008,7:187 210. Abe K. Neuroprotective therapy for ischemic stroke with free radical scavenger and gene stem cell therapy. Rinsho Shinkeigaku 2008,48:896 898. Adams PD. Regulation of the retinoblastoma tumor suppressor protein by cyclin/cdks. Biochim Biophys Acta 2001,1471:M123 133. Akiyama H, Ikeda K, Kondo H, McGeer PL.
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