Transporte Axonal y Neurodegeneración: Caminos que llevan a la Enfermedad de Alzheimer

FALZONE T

Bs As

Simposio; Congreso Anual de la Asociación Argentina de Alzheimer; 2015

Asociación Argentina de Alzheimer

Extreme polarized neurons depend on a regulated system of vesicle and protein delivery. Anterograde and retrograde axonal transport mediated by kinesin and dynein motors ensures the correct distribution of neuronal cargos supporting polarization. Abnormal protein accumulation together with ubiquitin proteasome degradation defects have been suggested as mechanism involved in the progression of Alzheimer disease (AD). To test the hypothesis that delivery defects of the protein degradative machinery may lead to the accumulation of toxic proteins in AD, we assessed for the movement of the proteasome. Live imaging experiments tracking fluorescent proteasome subunit revealed processive anterograde and retrograde trajectories compatible with motor dependent fast axonal transport. Interestingly, proteasome inhibition (MG132) induced selective changes in retrograde transport. Double color tracking proteasomes and lisosomes revealed a coordinated retrograde transport that is reduced by MG132. Moreover, MG132 induced kinesin-1 motor accumulation at growth cones and kinesin-1 reduction by siRNA increases lisosomal transport. Taken together, our results suggest a mechanism of crosstalk between proteasome and lisosome degradation that may be mediated by local accumulation of kinesin-1 motor