Alpha synuclein Target Validation

The majority of therapies for human disease involve the inhibition of a particular target important for pathogenesis. Many clinical trials fail because the target itself is not a critical component of disease. As a result, pharmaceutical companies
now demand more-stringent target-validation studies. Pathologic evidence from human PD tissue nominating a-syn as the primary agent of pathogenesis is circumstantial, whereas
human genetic studies firmly place the causative basis with asyn, but only in a very small proportion of familial and early onset- disease cases. The idea that a-syn is a robust therapeutic target in PD is provocative but nonetheless requires extensive
proof from target-validation studies. More than a decade of research centered on a-syn highlights outstanding questions through the descriptions of numerous model systems.