| Literature DB >> 11733371 |
P J Kahle1, M Neumann, L Ozmen, V Müller, S Odoy, N Okamoto, H Jacobsen, T Iwatsubo, J Q Trojanowski, H Takahashi, K Wakabayashi, N Bogdanovic, P Riederer, H A Kretzschmar, C Haass.
Abstract
alpha-Synuclein (alpha-SYN) is deposited in intraneuronal cytoplasmic inclusions (Lewy bodies, LBs) characteristic for Parkinson's disease (PD) and LB dementias. alpha-SYN forms LB-like fibrils in vitro, in contrast to its homologue beta-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]alpha-SYN driven by the brain neuron-specific promoter, Thy1. Distinct alpha-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 alpha-SYN was observed in brains of transgenic mice. In contrast, neither endogenous mouse alpha-SYN nor beta-SYN were detected in detergent-insoluble fractions from transgenic mouse brains. The nonamyloidogenic beta-SYN was incapable of forming insoluble fibrils because amino acids 73 to 83 in the central region of alpha-SYN are absent in beta-SYN. In conclusion, the specific accumulation of detergent-insoluble alpha-SYN in transgenic mice recapitulates a pivotal feature of human LB diseases.Entities:
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Year: 2001 PMID： 11733371 PMCID： PMC1850592 DOI： 10.1016/s0002-9440(10)63072-6
Source DB: PubMed Journal: Am J Pathol ISSN： 0002-9440 Impact factor: 4.307