Discovery of a Proneurogenic, Neuroprotective Chemical

Andrew A. Pieper, Shanhai Xie, Emanuela Capota, Sandi Jo Estill, Jeannie Zhong, Jeffrey M. Long, Ginger L. Becker, Paula Huntington, Shauna E. Goldman, Ching Han Shen, Maria Capota, Jeremiah K. Britt, Tiina Kotti, Kerstin Ure, Daniel J. Brat, Noelle S Williams, Karen S. MacMillan, Jacinth Naidoo, Lisa Melito, Jenny Hsieh & 3 others Jef K De Brabander, Joseph M Ready, Steven L McKnight

Research output: Contribution to journalArticle

211 Citations (Scopus)

Abstract

An in vivo screen was performed in search of chemicals capable of enhancing neuron formation in the hippocampus of adult mice. Eight of 1000 small molecules tested enhanced neuron formation in the subgranular zone of the dentate gyrus. Among these was an aminopropyl carbazole, designated P7C3, endowed with favorable pharmacological properties. In vivo studies gave evidence that P7C3 exerts its proneurogenic activity by protecting newborn neurons from apoptosis. Mice missing the gene encoding neuronal PAS domain protein 3 (NPAS3) are devoid of hippocampal neurogenesis and display malformation and electrophysiological dysfunction of the dentate gyrus. Prolonged administration of P7C3 to npas3-/- mice corrected these deficits by normalizing levels of apoptosis of newborn hippocampal neurons. Prolonged administration of P7C3 to aged rats also enhanced neurogenesis in the dentate gyrus, impeded neuron death, and preserved cognitive capacity as a function of terminal aging. PaperClip:

Original languageEnglish (US)
Pages (from-to)39-51
Number of pages13
JournalCell
Volume142
Issue number1
DOIs
StatePublished - Jul 2010

Fingerprint

Neurons
Dentate Gyrus
Neurogenesis
Apoptosis
Gene encoding
Rats
Hippocampus
Aging of materials
Display devices
Pharmacology
Molecules
Genes
Proteins

Keywords

  • Chembio
  • Molneuro

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pieper, A. A., Xie, S., Capota, E., Estill, S. J., Zhong, J., Long, J. M., ... McKnight, S. L. (2010). Discovery of a Proneurogenic, Neuroprotective Chemical. Cell, 142(1), 39-51. https://doi.org/10.1016/j.cell.2010.06.018

Discovery of a Proneurogenic, Neuroprotective Chemical. / Pieper, Andrew A.; Xie, Shanhai; Capota, Emanuela; Estill, Sandi Jo; Zhong, Jeannie; Long, Jeffrey M.; Becker, Ginger L.; Huntington, Paula; Goldman, Shauna E.; Shen, Ching Han; Capota, Maria; Britt, Jeremiah K.; Kotti, Tiina; Ure, Kerstin; Brat, Daniel J.; Williams, Noelle S; MacMillan, Karen S.; Naidoo, Jacinth; Melito, Lisa; Hsieh, Jenny; De Brabander, Jef K; Ready, Joseph M; McKnight, Steven L.

In: Cell, Vol. 142, No. 1, 07.2010, p. 39-51.

Research output: Contribution to journalArticle

Pieper, AA, Xie, S, Capota, E, Estill, SJ, Zhong, J, Long, JM, Becker, GL, Huntington, P, Goldman, SE, Shen, CH, Capota, M, Britt, JK, Kotti, T, Ure, K, Brat, DJ, Williams, NS, MacMillan, KS, Naidoo, J, Melito, L, Hsieh, J, De Brabander, JK, Ready, JM & McKnight, SL 2010, 'Discovery of a Proneurogenic, Neuroprotective Chemical', Cell, vol. 142, no. 1, pp. 39-51. https://doi.org/10.1016/j.cell.2010.06.018
Pieper AA, Xie S, Capota E, Estill SJ, Zhong J, Long JM et al. Discovery of a Proneurogenic, Neuroprotective Chemical. Cell. 2010 Jul;142(1):39-51. https://doi.org/10.1016/j.cell.2010.06.018
Pieper, Andrew A. ; Xie, Shanhai ; Capota, Emanuela ; Estill, Sandi Jo ; Zhong, Jeannie ; Long, Jeffrey M. ; Becker, Ginger L. ; Huntington, Paula ; Goldman, Shauna E. ; Shen, Ching Han ; Capota, Maria ; Britt, Jeremiah K. ; Kotti, Tiina ; Ure, Kerstin ; Brat, Daniel J. ; Williams, Noelle S ; MacMillan, Karen S. ; Naidoo, Jacinth ; Melito, Lisa ; Hsieh, Jenny ; De Brabander, Jef K ; Ready, Joseph M ; McKnight, Steven L. / Discovery of a Proneurogenic, Neuroprotective Chemical. In: Cell. 2010 ; Vol. 142, No. 1. pp. 39-51.
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