ApoE Receptor 2 Controls Neuronal Survival in the Adult Brain

Uwe Beffert, Farnas Nematollah Farsian, Irene Masiulis, Robert E Hammer, Sung Ok Yoon, Klaus M. Giehl, Joachim Herz

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

A central pathogenic feature of neurodegenerative diseases and neurotrauma is the death of neurons. A mechanistic understanding of the factors and conditions that induce the dysfunction and death of neurons is essential for devising effective treatment strategies against neuronal loss after trauma or during aging. Because Apolipoprotein E (ApoE) is a major risk factor for several neurodegenerative diseases, including Alzheimer's disease [1], a direct or indirect role of ApoE receptors in the disease process is likely. Here we have used gene targeting in mice to investigate possible roles of ApoE receptors in the regulation of neuronal survival. We demonstrate that a differentially spliced isoform of an ApoE receptor, ApoE receptor 2 (Apoer2), is essential for protection against neuronal cell loss during normal aging. Furthermore, the same splice form selectively promotes neuronal cell death after injury through mechanisms that may involve serine/threonine kinases of the Jun N-terminal kinase (JNK) family. These findings raise the possibility that ApoE and its receptors cooperatively regulate common mechanisms that are essential to neuronal survival in the adult brain.

Original languageEnglish (US)
Pages (from-to)2446-2452
Number of pages7
JournalCurrent Biology
Volume16
Issue number24
DOIs
StatePublished - Dec 19 2006

Keywords

  • MOLNEURO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Beffert, U., Nematollah Farsian, F., Masiulis, I., Hammer, R. E., Yoon, S. O., Giehl, K. M., & Herz, J. (2006). ApoE Receptor 2 Controls Neuronal Survival in the Adult Brain. Current Biology, 16(24), 2446-2452. https://doi.org/10.1016/j.cub.2006.10.029