Microtubule dysfunction in experimental model of Parkinson's disease

Dysfunction of axonal transport is a common theme in many neurodegenerative disease, and recent data show that MPP+, a well known parkinsonism-inducing neurotoxin, causes an early defect of fast axonal transport. Alterations of axonal transport could be easily explained by microtubule (MT) dysfunctions, because MTs are the railways along proteins and organelles move. Starting from the notion that MT are a common target of toxins and mutated proteins inducing Parkinson’s disease, and knowing that MPP+ alters MT polymerization and dynamics in vitro, we investigated the relationship between MT dynamics and axonal transport in PC12 cells exposed to MPP+ and in mice treated with MPTP, the metabolic precursor of MPP+. Combining Fluorescence Recovery After Photobleaching (FRAP) analyses and live cell imaging, we observed that MPP+ causes a reduction of MT dynamics and a reorientation of MTs before axonal transport impairment occurs. By using indirect approaches, as western blotting and immunofluorescence analyses, we found that in mice striata MPTP leads to an unbalance of dynamic and stable MTs, before that mitochondria accumulations became noticeable. Taken together, live cell imaging and in vivo analyses show that MT dysfunctions precede axonal transport impairment in the MPTP model of Parkinson’s disease.