Microtubule dysfunction precedes transport impairment and mitochondria damage in MPP+-induced neurodegeneration

摘要: J. Neurochem. (2010) 115, 247–258. Abstract Dysfunction of the microtubule (MT) system is an emerging theme in pathogenesis Parkinson’s disease. This study was designed to investigate putative role MT dysfunction dopaminergic neuron death induced by neurotoxin 1-methyl-4-phenylpiridinium (MPP+). In nerve growth factor-differentiated PC12 cells, we have analyzed post-translational modifications tubulin known be associated with differently dynamic MTs and show that MPP+ causes a selective loss concomitant enrichment stable MTs. Through direct live cell imaging approach, significant reduction dynamics following exposure reorientation Furthermore, these alterations precede impairment intracellular transport as revealed changes mitochondria movements along neurites their accumulation into varicosities. We also activation caspase 3 mitochondrial injury, well-known MPP+, found they are noticeable only when already established. These data provide first evidence axonal damage might consequence MPP+-induced neurodegeneration, lending support concept organization could play pivotal neuronal