LAUSR

Aggresomes are closely related to Lewy bodies (LBs), structures whose presence is a hallmark of Parkinson’s disease. LBs are related to aggresomes. A major constituent of these LBs is alpha synuclein, the gene for which is mutated in the inherited form of Parkinson’s. The cellular location of aggresomes coincides with that of the centrosome, the microtubule organising centre of the cell. Since the aggresome is positioned in close proximity to and shares components with the centrosome, it is possible that it hinders centrosomal function. In this study we sought to test if any functions of the centrosome were impeded by the presence of aggresomes in their close vicinity. Several cell lines including SH-SH5Y, HeLa cells and primary rat neurons were treated to induce aggresomes. This was achieved either by exposure to the proteasome inhibitor MG-132 or by transfection with alpha synuclein overexpression constructs. Centrosome function was assessed by microtubule regrowth, wound healing and ciliogenesis assay. Similarly zebrafish embryos were exposed to MG-132 were cilia at the olfactory neurons were stained for. We show here that aggresomes severely compromise centrosome function. Microtubule nucleation is severely reduced and the centrosome is unable to be repositioned during cell migration. We also show that aggresomes can prevent a cell from turning its centrosome into a cilium. Also in zebrafish embryos number of cilia in the olfactory epithelium is severely reduced. Defects in the generation and organisation of the microtubule network would be predicted to affect intracellular transport including vesicular trafficking of neurotransmitter transport. An early symptom of Parkinson’s is loss of smell and anosmia. It maybe possible this symptom is a result of loss of cilia from olfactory neurons. If this is the case, then cilia density in the olfactory epithelium of Parkinson’s patients should be reduced in age matched controls.