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Two C-terminal sequence variations determine differential neurotoxicity between human and mouse α-synuclein.

Natalie LandeckKatherine E StrathearnDaniel YsselsteinKerstin BuckSayan DuttaSiddhartha BanerjeeZhengjian LvJohn D HullemanJagadish HindupurLi-Kai LinSonal PadalkarLia A StanciuYuri L LyubchenkoDeniz KirikJean-Christophe Rochet
Published in: Molecular neurodegeneration (2020)
Mouse aSyn is less neurotoxic than the human A53T variant as a result of inhibitory effects of two C-terminal amino acid substitutions on membrane-induced aSyn aggregation and aSyn-mediated vesicle permeabilization. Our findings highlight the importance of membrane-induced self-assembly in aSyn neurotoxicity and suggest that inhibiting this process by targeting the C-terminal domain could slow neurodegeneration in PD and other synucleinopathy disorders.
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