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Progranulin protect...
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Minami, S. Sakura
(author)
Progranulin protects against amyloid beta deposition and toxicity in Alzheimer's disease mouse models
- Article/chapterEnglish2014
Publisher, publication year, extent ...
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2014-09-28
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Springer Science and Business Media LLC,2014
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:su-160586
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-160586URI
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https://doi.org/10.1038/nm.3672DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Haploinsufficiency of the progranulin (PGRN) gene (GRN) causes familial frontotemporal lobar degeneration (FTLD) and modulates an innate immune response in humans and in mouse models. GRN polymorphism may be linked to late-onset Alzheimer's disease (AD). However, the role of PGRN in AD pathogenesis is unknown. Here we show that PGRN inhibits amyloid beta (A beta) deposition. Selectively reducing microglial expression of PGRN in AD mouse models impaired phagocytosis, increased plaque load threefold and exacerbated cognitive deficits. Lentivirus-mediated PGRN overexpression lowered plaque load in AD mice with aggressive amyloid plaque pathology. A beta plaque load correlated negatively with levels of hippocampal PGRN, showing the dose-dependent inhibitory effects of PGRN on plaque deposition. PGRN also protected against A beta toxicity. Lentivirus-mediated PGRN overexpression prevented spatial memory deficits and hippocampal neuronal loss in AD mice. The protective effects of PGRN against A beta deposition and toxicity have important therapeutic implications. We propose enhancing PGRN as a potential treatment for PGRN-deficient FTLD and AD.
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Min, Sang-Won
(author)
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Krabbe, Grietje
(author)
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Wang, Chao
(author)
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Zhou, Yungui
(author)
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Asgarov, RustamStockholms universitet,Institutionen för neurokemi
(author)
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Li, Yaqiao
(author)
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Martens, Lauren H.
(author)
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Elia, Lisa P.
(author)
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Ward, Michael E.
(author)
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Mucke, Lennart
(author)
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Farese, Robert V.
(author)
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Gan, Li
(author)
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Stockholms universitetInstitutionen för neurokemi
(creator_code:org_t)
Related titles
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In:Nature Medicine: Springer Science and Business Media LLC20:10, s. 1157-11641078-89561546-170X
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Minami, S. Sakur ...
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Min, Sang-Won
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Krabbe, Grietje
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Wang, Chao
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Zhou, Yungui
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Asgarov, Rustam
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show more...
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Li, Yaqiao
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Martens, Lauren ...
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Elia, Lisa P.
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Ward, Michael E.
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Mucke, Lennart
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Farese, Robert V ...
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Gan, Li
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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Nature Medicine
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Stockholm University