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Distinct α-synuclein strains differentially promote tau inclusions in neurons.
Guo, Jing L; Covell, Dustin J; Daniels, Joshua P; Iba, Michiyo; Stieber, Anna; Zhang, Bin; Riddle, Dawn M; Kwong, Linda K; Xu, Yan; Trojanowski, John Q; Lee, Virginia M Y.
Afiliação
  • Guo JL; Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Cell ; 154(1): 103-17, 2013 Jul 03.
Article em En | MEDLINE | ID: mdl-23827677
Many neurodegenerative diseases are characterized by the accumulation of insoluble protein aggregates, including neurofibrillary tangles comprised of tau in Alzheimer's disease and Lewy bodies composed of α-synuclein in Parkinson's disease. Moreover, different pathological proteins frequently codeposit in disease brains. To test whether aggregated α-synuclein can directly cross-seed tau fibrillization, we administered preformed α-synuclein fibrils assembled from recombinant protein to primary neurons and transgenic mice. Remarkably, we discovered two distinct strains of synthetic α-synuclein fibrils that demonstrated striking differences in the efficiency of cross-seeding tau aggregation, both in neuron cultures and in vivo. Proteinase K digestion revealed conformational differences between the two synthetic α-synuclein strains and also between sarkosyl-insoluble α-synuclein extracted from two subgroups of Parkinson's disease brains. We speculate that distinct strains of pathological α-synuclein likely exist in neurodegenerative disease brains and may underlie the tremendous heterogeneity of synucleinopathies.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Proteínas tau / Alfa-Sinucleína / Neurônios Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Proteínas tau / Alfa-Sinucleína / Neurônios Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2013 Tipo de documento: Article