alpha-Synuclein A53T substitution associated with Parkinson disease also marks the divergence of Old World and New World primates.
The alpha-synuclein mutation Ala53Thr is associated with increased oligomerization, toxicity, and early onset Parkinson disease in humans, but 53Thr is the normal residue in other species. Comparative sequencing of SNCA genes shows that 53Ala marks the divergence of Old World and New World primates, in an otherwise constrained protein region. These results have implications for interpreting Parkinson disease models and suggest that other long-lived mammals have different mechanisms to forestall alpha-synucleinopathy.
Hamilton
Bruce A
BA
Department of Medicine and Department of Cellular and Molecular Medicine, University of California at San Diego School of Medicine, La Jolla, CA 92093-0644, USA. bah@ucsd.edu
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002427:Cebidae; D002520:Cercopithecidae; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D051843:Synucleins; D051844:alpha-Synuclein