Inhibition of dynactin leads to retrograde axonal transport dysfunction, α-synuclein and autophagosome aggregation in parkinsonian Zebrafish

Bingyin Su

Development and Regeneration Key Lab of Sichuan Province, Department of Histology and Embryology, Department of Pathology, Chengdu Medical College, Chengdu, China

To test whether dynactin is involved in the retrograde degeneration of dopaminergic neurons which results in PD. Mycalolide B was used to inhibit the expression of dynactin in Tg (Vmat²:GFP) zebrafish. Dynactin-siRNA knockdown was performed in SH-SY⁵Y cells and the anterograde and retrograde axonal transport and the autophagy pathway were investigated. Dynactin knockdown resulted in PD-like symptoms. Retrograde, but not anterograde axonal transport was blocked. An abnormal accumulation of α-synuclein in the diencephalon was detected. The distribution of dynein changed, accompanied by the formation of numerous autophagosomes. The results indicate that inhibition of dynactin lead to retrograde axonal transport dysfunction, α-synuclein specific aggregation, and result in an increase in autophagosome aggregation and a series of pathological changes in dopaminergic neuron degeneration.