Novel animal model defines genetic contributions for neuron-to-neuron transfer of alpha-synuclein

作者：Tyson Trevor; Senchuk Megan; Cooper Jason F; George Sonia; Van Raamsdonk Jeremy M; Brundin Patrik

来源：Scientific Reports, 2017, 7(1): 7506.

DOI：10.1038/s41598-017-07383-6

<jats:title>Abstract</jats:title><jats:p>Cell-to-cell spreading of misfolded α-synuclein (α-syn) is suggested to contribute to the progression of neuropathology in Parkinson’s disease (PD). Compelling evidence supports the hypothesis that misfolded α-syn transmits from neuron-to-neuron and seeds aggregation of the protein in the recipient cells. Furthermore, α-syn frequently appears to propagate in the brains of PD patients following a stereotypic pattern consistent with progressive spreading along anatomical pathways. We have generated a <jats:italic>C. elegans</jats:italic> model that mirrors this progression and allows us to monitor α-syn neuron-to-neuron transmission in a live animal over its lifespan. We found that modulation of autophagy or exo/endocytosis, affects α-syn transfer. Furthermore, we demonstrate that silencing <jats:italic>C. elegans</jats:italic> orthologs of PD-related genes also increases the accumulation of α-syn. This novel worm model is ideal for screening molecules and genes to identify those that modulate prion-like spreading of α-syn in order to target novel strategies for disease modification in PD and other synucleinopathies.</jats:p>

• 出版日期2017-8-8