The intrinsically disordered protein α-synuclein (aSN) forms insoluble aggregates in the brains of Parkinson's Disease patients. Cytotoxicity is attributed to a soluble aSN oligomeric species which permeabilizes membranes significantly more than monomers and fibrils. In humans, the mutation A53T induces early-onset PD and increases aSN oligomerization and fibrillation propensity, but Thr53 occurs naturally in aSN of most animals. We compared aSN from elephant, bowhead whale and pig with human aSN. While all three animal aSN showed significantly reduced fibrillation behavior, elephant aSN formed much more oligomer, and pig aSN much less, than human aSN. However, all animal aSN oligomers showed decreased permeabilization towards anionic lipid vesicles, indicative of lowered cytotoxicity. These animal aSN share three substitutions compared to human aSN: A53T, G68E and V95G. We analyzed aggregation and membrane binding of all 8 mutants combining these three mutations. While G68E is particularly important in reducing the fibrillation and possible toxicity, the greatest effect is seen when all three mutations are present. Thus a small number of mutations can significantly reduce aSN toxicity.