Effect of α-synuclein on membrane permeability and synaptic transmission: a clue to neurodegeneration?

This is an Editorial highlighting the article "Extracellular α-synuclein alters synaptic transmission in rain neurons by perforating the neuronal plasma membrane" by Pacheco and coauthors, in this issue of Journal of Neurochemistry. The authors demonstrate, using a variety of techniques, that alpha-synuclein possesses neurotoxicity toward brain neuronal plasma membranes exposed directly to extracellular alpha-synuclein oligomers. Extracellular oligomeric α-synuclein rapidly associates to hippocampal membranes and induces pore formation in the hippocampal cells. This increases membrane conductance and calcium influx. Oligomeric α-synuclein also induces changes in synaptic current activity in hippocampal neurons. The authors' findings support the pathogenic role of extracellular alpha-synuclein in the brain, and should provide a new strategy for the treatment of Parkinson's disease and other synucleinopathies, neurodegenerative diseases with aberrant accumulation of aggregated alpha-synuclein in neurons, nerve fibers or glial cells. Read the full article 'Extracellular α-synuclein alters synaptic transmission in brain neurons by perforating the neuronal plasma membrane' on page 731.