Regulators of protein misfolding and aggregation and methods...

G - Physics – 01 – N

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G01N 33/53 (2006.01) A01K 67/00 (2006.01) A61K 31/00 (2006.01) C12Q 1/68 (2006.01)

Patent

CA 2599182

Polynucleotide molecules and the proteins encoded by the molecules, diagnostic and treatment methods for neurological disorders characterized by protein aggregation are provided. Genes are described herein that affect the misfolding of, and subsequent aggregation of, aggregation-prone proteins such as alpha-synuclein and have implications for the diagnosis and treatment of neurological diseases related to protein aggregation such as Parkinson's disease. Knockdown of expression of the genes described herein using RNAi results in alpha-synuclein protein aggregation in a C. elegans model of protein aggregation. Dopaminergic neuroprotection after exposure to the neurotoxin 6-OHDA or overexpression of alpha-synuclein may also be provided by overexpression of proteins. Knowledge of genes relating to protein misfolding and aggregation provides powerful means to develop diagnostic screening methods, mutation analysis and drug design information for the development of novel therapeutic and neuroprotective compounds to treat neurodegenerative diseases such as Parkinson's disease.

Molécules polynucléotidiques et protéines codées par elles, procédés de diagnostic et de traitement pour troubles neurologiques caractérisés par une agrégation de protéines. On décrit des gènes qui affectent le mauvais repliement puis l'agrégation de protéines à tendance agrégative, du type alpha-synucléine, et qui ont des répercussions sur le diagnostic et le traitement de maladies neurologiques liées à l'agrégation de protéines comme la maladie de Parkinson. En supprimant l'expression des gènes décrits par le biais d'ARNi, on induit une agrégation de protéine alpha-synucléine dans un modèle C. elegans d'agrégation de protéine. On peut aussi assurer une neuroprotection dopaminergique après exposition à la neurotoxine 6-OHDA ou une surexpression d'alpha-synucléine par surexpression de protéines. La connaissance de gènes se rapportant au mauvais repliement et à l'agrégation des protéines constitue un moyen puissant de développement de procédés d'analyse diagnostique, de développement d'analyse de mutation et d'information permettant l'élaboration de médicaments, en vue de l'élaboration de composés thérapeutiques et neuroprotecteurs qui permettent de traiter les maladies neurodégénératives comme la maladie de Parkinson.

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