Discussion
What species of alpha-synuclein should be targeted for development of PD therapies?
Current theory suggests a possible toxic oligomeric or aggregated form of alpha-synuclein as the trigger for subsequent neurodegeneration in PD, but definitive evidence for this is lacking. Proposed therapeutic approaches focus predominately on breaking up aggregates, or attempt to reduce alpha-synuclein protein levels, either by inhibiting production (e.g, via RNA interference) or enhancing protein turnover. Given current understanding of alpha-synuclein, are these the best approaches for targeting alpha-synuclein therapeutically? What studies are needed to clarify the ideal alpha-synuclein target?
Responses:
Catch me if you can: the ...
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Alpha-synuclein S129 ...
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Chen L, Feany MB. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci. 2005;8(5):657-63.
Azeredo da Silveira S, Schneider BL, Cifuentes-Diaz C, Sage D, Abbas-Terki T, Iwatsubo T, et al. Phosphorylation does not prompt, nor prevent, the formation of alpha-synuclein toxic species in a rat model of Parkinson's disease. Hum Mol Genet. 2009;18(5):872-87.
Inglis KJ, Chereau D, Brigham EF, Chiou SS, Schöbel S, Frigon NL, et al. Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system. J Biol Chem. 2009;284(5):2598-602.
What species of ...
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one more Question
Alpha-synuclein ...
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