Notch: From neural development to neurological disorders

Justin D. Lathia, Mark P. Mattson, Aiwu Cheng

Research output: Contribution to journalArticle

Abstract

Notch is an integral membrane protein that functions as receptor for ligands such as jagged and delta that are associated with the surface of neighboring cells. Upon ligand binding, notch is proteolytically cleaved within its transmembrane domain by presenilin-1 (the enzymatic component of the γ-secretase complex) resulting in the release of a notch intracellular domain which translocates to the nucleus where it regulates gene expression. Notch signaling plays multiple roles in the development of the CNS including regulating neural stem cell (NSC) proliferation, survival, self-renewal and differentiation. Notch is also present in post-mitotic neurons in the adult CNS wherein its activation influences structural and functional plasticity including processes involved in learning and memory. Recent findings suggest that notch signaling in neurons, glia, and NSCs may be involved in pathological changes that occur in disorders such as stroke, Alzheimer's disease and CNS tumors. Studies of animal models suggest the potential of agents that target notch signaling as therapeutic interventions for several different CNS disorders.

Original languageEnglish (US)
Pages (from-to)1471-1481
Number of pages11
JournalJournal of Neurochemistry
Volume107
Issue number6
DOIs
StatePublished - Dec 2008
Externally publishedYes

Keywords

  • Brain ischemia and neurodegeneration
  • Development
  • Neural stem cells
  • Notch
  • Synaptic plasticity

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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