Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of SNCA mRNA in a cell or animal, and in certain instances reducing the amount of alpha-synuclein protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include motor dysfunction, aggregation of alpha-synuclein, neurodegeneration, cognitive decline and dementia. Such neurodegenerative diseases include Parkinson’s disease, dementia with Lewy bodies, diffuse Lewy body disease, pure autonomic failure, multiple system atrophy, neuronopathic Gaucher's disease and Alzheimer’s disease.本發明提供用於降低細胞或動物中之SNCA mRNA之量或活性，且在某些情況下降低細胞或動物中之α-突觸核蛋白之量的化合物、方法及醫藥組合物。此類化合物、方法及醫藥組合物適用於改善神經退行性疾病之至少一種症狀或標誌。此類症狀及標誌包括運動功能障礙、α-突觸核蛋白聚集、神經變性、認知功能減退及癡呆。此類神經退行性疾病包括帕金森氏病、路易體癡呆、彌漫性路易體病、單純自主神經衰竭、多系統萎縮症、神經元性高歇氏病及阿茨海默氏病。
