Reelin protects against amyloid β toxicity in vivo.

Autor:	Lane-Donovan C; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. joachim.herz@utsouthwestern.edu courtney.lane@utsouthwestern.edu., Philips GT; Center for Neural Science, New York University, New York, NY 10003, USA., Wasser CR; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Durakoglugil MS; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Masiulis I; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Upadhaya A; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Pohlkamp T; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Center for Neuroscience, Department of Neuroanatomy, Albert-Ludwigs-University, Freiburg 79085, Germany., Coskun C; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Kotti T; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Steller L; Institute for Structural Neurobiology, Center for Molecular Neurobiology, Hamburg 20251, Germany., Hammer RE; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Frotscher M; Institute for Structural Neurobiology, Center for Molecular Neurobiology, Hamburg 20251, Germany., Bock HH; Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University, Düsseldorf 40225, Germany., Herz J; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Center for Neuroscience, Department of Neuroanatomy, Albert-Ludwigs-University, Freiburg 79085, Germany. Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. joachim.herz@utsouthwestern.edu courtney.lane@utsouthwestern.edu.
Jazyk:	angličtina
Zdroj:	Science signaling [Sci Signal] 2015 Jul 07; Vol. 8 (384), pp. ra67. Date of Electronic Publication: 2015 Jul 07.
DOI:	10.1126/scisignal.aaa6674
Abstrakt:	Alzheimer's disease (AD) is a currently incurable neurodegenerative disorder and is the most common form of dementia in people over the age of 65 years. The predominant genetic risk factor for AD is the ε4 allele encoding apolipoprotein E (ApoE4). The secreted glycoprotein Reelin enhances synaptic plasticity by binding to the multifunctional ApoE receptors apolipoprotein E receptor 2 (Apoer2) and very low density lipoprotein receptor (Vldlr). We have previously shown that the presence of ApoE4 renders neurons unresponsive to Reelin by impairing the recycling of the receptors, thereby decreasing its protective effects against amyloid β (Aβ) oligomer-induced synaptic toxicity in vitro. We showed that when Reelin was knocked out in adult mice, these mice behaved normally without overt learning or memory deficits. However, they were strikingly sensitive to amyloid-induced synaptic suppression and had profound memory and learning disabilities with very low amounts of amyloid deposition. Our findings highlight the physiological importance of Reelin in protecting the brain against Aβ-induced synaptic dysfunction and memory impairment. (Copyright © 2015, American Association for the Advancement of Science.)
Databáze:	MEDLINE
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