Selective Insolubility of -Synuclein in Human Lewy Body Diseases Is Recapitulated in a Transgenic Mouse Model
Identifieur interne : 001955 ( Main/Exploration ); précédent : 001954; suivant : 001956Selective Insolubility of -Synuclein in Human Lewy Body Diseases Is Recapitulated in a Transgenic Mouse Model
Auteurs : Philipp J. Kahle [Allemagne] ; Manuela Neumann ; Laurence Ozmen ; Veronika Mller ; Sabine Odoy ; Noriko Okamoto ; Helmut Jacobsen ; Takeshi Iwatsubo ; John Q. Trojanowski ; Hitoshi Takahashi ; Koichi Wakabayashi ; Nenad Bogdanovic ; Peter Riederer ; Hans A. Kretzschmar ; Christian HaassSource :
- The American Journal of Pathology [ 0002-9440 ] ; 2001.
Abstract
-Synuclein (-SYN) is deposited in intraneuronal cytoplasmic inclusions (Lewy bodies, LBs) characteristic for Parkinsons disease (PD) and LB dementias. -SYN forms LB-like fibrils in vitro, in contrast to its homologue -SYN. Here we have investigated the solubility of SYNs in human LB diseases and in transgenic mice expressing human wild-type and PD-associated mutant [A30P]-SYN driven by the brain neuron-specific promoter, Thy1. Distinct -SYN species were detected in the detergent-insoluble fractions from brains of patients with PD, dementia with LBs, and neurodegeneration with brain iron accumulation type 1 (formerly known as Hallervorden-Spatz disease). Using the same extraction method, detergent-insolubility of human -SYN was observed in brains of transgenic mice. In contrast, neither endogenous mouse -SYN nor -SYN were detected in detergent-insoluble fractions from transgenic mouse brains. The nonamyloidogenic -SYN was incapable of forming insoluble fibrils because amino acids 73 to 83 in the central region of -SYN are absent in -SYN. In conclusion, the specific accumulation of detergent-insoluble -SYN in transgenic mice recapitulates a pivotal feature of human LB diseases.
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DOI: 10.1016/S0002-9440(10)63072-6
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Here we have investigated the solubility of SYNs in human LB diseases and in transgenic mice expressing human wild-type and PD-associated mutant [A30P]-SYN driven by the brain neuron-specific promoter, Thy1. Distinct -SYN species were detected in the detergent-insoluble fractions from brains of patients with PD, dementia with LBs, and neurodegeneration with brain iron accumulation type 1 (formerly known as Hallervorden-Spatz disease). Using the same extraction method, detergent-insolubility of human -SYN was observed in brains of transgenic mice. In contrast, neither endogenous mouse -SYN nor -SYN were detected in detergent-insoluble fractions from transgenic mouse brains. The nonamyloidogenic -SYN was incapable of forming insoluble fibrils because amino acids 73 to 83 in the central region of -SYN are absent in -SYN. 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Kretzschmar</name><name sortKey="Mller, Veronika" sort="Mller, Veronika" uniqKey="Mller V" first="Veronika" last="Mller">Veronika Mller</name><name sortKey="Neumann, Manuela" sort="Neumann, Manuela" uniqKey="Neumann M" first="Manuela" last="Neumann">Manuela Neumann</name><name sortKey="Odoy, Sabine" sort="Odoy, Sabine" uniqKey="Odoy S" first="Sabine" last="Odoy">Sabine Odoy</name><name sortKey="Okamoto, Noriko" sort="Okamoto, Noriko" uniqKey="Okamoto N" first="Noriko" last="Okamoto">Noriko Okamoto</name><name sortKey="Ozmen, Laurence" sort="Ozmen, Laurence" uniqKey="Ozmen L" first="Laurence" last="Ozmen">Laurence Ozmen</name><name sortKey="Riederer, Peter" sort="Riederer, Peter" uniqKey="Riederer P" first="Peter" last="Riederer">Peter Riederer</name><name sortKey="Takahashi, Hitoshi" sort="Takahashi, Hitoshi" uniqKey="Takahashi H" first="Hitoshi" last="Takahashi">Hitoshi Takahashi</name><name sortKey="Trojanowski, John Q" sort="Trojanowski, John Q" uniqKey="Trojanowski J" first="John Q." last="Trojanowski">John Q. Trojanowski</name><name sortKey="Wakabayashi, Koichi" sort="Wakabayashi, Koichi" uniqKey="Wakabayashi K" first="Koichi" last="Wakabayashi">Koichi Wakabayashi</name></noCountry><country name="Allemagne"><noRegion><name sortKey="Kahle, Philipp J" sort="Kahle, Philipp J" uniqKey="Kahle P" first="Philipp J." last="Kahle">Philipp J. Kahle</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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