Threonine 53 in alpha-synuclein is conserved in long-living non-primate animals.
Alpha-synuclein is the main constituent of Lewy bodies in familial and sporadic cases of Parkinson's disease (PD). Autosomal dominant point mutations, gene duplications or triplications in the alpha-synuclein (SNCA) gene cause hereditary forms of PD. One of the alpha-synuclein point mutations, Ala53Thr, is associated with increased oligomerization toxicity leading to familial early-onset PD in humans. The amino acid in position 53 in alpha-synuclein is an alanine in humans, great apes and Old World primates. However, this amino acid is a threonine in the alpha-synuclein of all other examined species, including New World monkeys. Here, we present DNA sequence analysis of SNCA and the deduced amino acid sequences of alpha-synuclein cloned from various different species, ranging from fish to mammals, which are known for their long-living potential. In all these investigated species the 53Thr is found. We conclude that 53Thr is not a molecular adaptation for long-living animals to minimize the risk of developing PD.
Larsen
Knud
K
Department of Genetics and Biotechnology, Faculty of Agricultural Sciences, University of Aarhus, Blichers Alle 20, Tjele, Denmark. Knud.Larsen@agrsci.dk
Hedegaard
Claus
C
Bertelsen
Mads Frost
MF
Bendixen
Christian
C
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D008136:Longevity; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013912:Threonine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D051844:alpha-Synuclein; D013912:Threonine