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Abstract

It is demonstrated that alpha synculein toxicity such as α-synuclein mediated cell death, and alpha synuclein induced reactive oxygen species (ROS) in a cell requires proapoptotic endonuclease G and that the deletion of the endonuclease G or suppressing of the endonuclease G apoptotic pathway attenuates or counteracts such alpha synuclein toxicity. In view of these observations, compositions and methods for inhibition of α-synuclein toxicity are provided. The inhibiting α-synuclein toxicity can be used in methods for the treatment of synucleinopathies, such as Parkinsons disease (PD), dementia with Lewy bodies (DLB), pure autonomic failure (PAF), and multiple system atroypy (MSA) and the manufacture of medicaments for such treatment. In particular, pharmaceutical compositions containing inhibitors of endonuclease G, and their use in the treatment of synucleinopathies such as Parkinson's disease, dementia with Lew bodies, pure autonomic failure, and multiple system atrophy and the manufacture of medicaments for such treatment are presented. In addition, methods for the identification of compounds for attenuating the synuclein toxicity are also provided.

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