Publikationsdatum:
2013-09-21
Beschreibung:
Soluble beta-amyloid (Abeta) oligomers impair synaptic plasticity and cause synaptic loss associated with Alzheimer's disease (AD). We report that murine PirB (paired immunoglobulin-like receptor B) and its human ortholog LilrB2 (leukocyte immunoglobulin-like receptor B2), present in human brain, are receptors for Abeta oligomers, with nanomolar affinity. The first two extracellular immunoglobulin (Ig) domains of PirB and LilrB2 mediate this interaction, leading to enhanced cofilin signaling, also seen in human AD brains. In mice, the deleterious effect of Abeta oligomers on hippocampal long-term potentiation required PirB, and in a transgenic model of AD, PirB not only contributed to memory deficits present in adult mice, but also mediated loss of synaptic plasticity in juvenile visual cortex. These findings imply that LilrB2 contributes to human AD neuropathology and suggest therapeutic uses of blocking LilrB2 function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853120/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853120/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Taeho -- Vidal, George S -- Djurisic, Maja -- William, Christopher M -- Birnbaum, Michael E -- Garcia, K Christopher -- Hyman, Bradley T -- Shatz, Carla J -- 5P50AG005134/AG/NIA NIH HHS/ -- 5R01AG041507/AG/NIA NIH HHS/ -- 5T32EY020485/EY/NEI NIH HHS/ -- EY02858/EY/NEI NIH HHS/ -- K08 NS069811/NS/NINDS NIH HHS/ -- K08NS069811/NS/NINDS NIH HHS/ -- NS069375/NS/NINDS NIH HHS/ -- R01 AG041507/AG/NIA NIH HHS/ -- R01 EY002858/EY/NEI NIH HHS/ -- R01 MH071666/MH/NIMH NIH HHS/ -- T32 EY020485/EY/NEI NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Sep 20;341(6152):1399-404. doi: 10.1126/science.1242077.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Bio-X, James H. Clark Center, Stanford University, Stanford, CA 94305, USA. tkim808@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24052308" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Alzheimer Disease/*physiopathology
;
Amyloid beta-Peptides/*metabolism/pharmacology
;
Animals
;
Disease Models, Animal
;
Female
;
HEK293 Cells
;
Hippocampus/physiopathology
;
Humans
;
Long-Term Potentiation
;
Male
;
Membrane Glycoproteins/genetics/*physiology
;
Mice
;
Mice, Transgenic
;
*Neuronal Plasticity
;
Peptide Fragments/*metabolism/pharmacology
;
Receptors, Immunologic/genetics/*physiology
;
Synapses/*physiology
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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