Truncated fragments of alpha-synuclein in lewy body disease

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 16/18 (2006.01) A01K 67/027 (2006.01) A61K 38/17 (2006.01) A61K 39/00 (2006.01) A61K 39/385 (2006.01) A61K 39/395 (2006.01) A61K 49/00 (2006.01) A61P 25/28 (2006.01) C12N 9/48 (2006.01) C12N 15/85 (2006.01) C12Q 1/00 (2006.01) C12Q 1/37 (2006.01) G01N 33/50 (2006.01) G01N 33/53 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2584512

The application identifies novel fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to full-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha- synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals.

L'invention concerne de nouveaux fragments d'.alpha.-synucléine chez des patients atteints de maladie à corps de Lewy (LBD), et des modèles animaux transgéniques de ces fragments. Ces maladies se caractérisent par des aggrégations d'.alpha.-synucléine. Ces fragments présentent une terminaison C tronquée par rapport à l'.alpha.-synucléine complète. Certains fragments se caractérisent par une masse moléculaire d'environ 12 kDa, mesurée par électrophorèse sur gel SDS dans un tampon de tricine, et par une troncation d'au moins dix acides aminés contigus à partir de la terminaison C de l'.alpha.-synucléine naturelle. Le site de clivage se présente de préférence après le résidu 117 et avant le résidu 126 de l'.alpha.-synucléine naturelle. L'identification de ces nouveaux fragments d'.alpha.-synucléine trouve plusieurs applications dans des domaines tels que découverte de médicaments, diagnostics, thérapies, et animaux transgéniques.

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