Abstract
An intriguing report by Dettmer et al. (1) in PNAS describes a link between the in vivo multimerization state of the neuronal protein α-synuclein (αSyn) and neurotoxicity. In this paper, it is demonstrated that αSyn mutations that abolish the formation of soluble αSyn tetramers in live neurons decrease αSyn solubility, induce αSyn-rich cytoplasmic inclusions, and cause neurotoxicity similar to that observed due to a known proapoptotic agent. The reporting authors form a convincing link between the presence of stable αSyn tetramers and neuron viability. With this discovery, it would seem that the controversy over the relevance (and indeed, the existence) of the physiological αSyn tetramer might be laid to rest (2⇓⇓–5).