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    Prion Disease Triggered by Impaired Transport in Neurons


    Intracerebral prion infection led to axonal transport impairments in 45 per cent of neurons in the red nucleus and up to 94 per cent of motor cortex neurons, according to a study by researchers of the University of Würzburg, published in PLoS Pathogens.

    In contrast to previous knowledge, the study shows that nervous system integrity and axonal properties may play a key role in prion diseases. The findings suggest novel targets for therapeutic and diagnostic approaches in the early stage of prion disease.

    In past years, prion diseases, such as BSE or variant Creutzfeldt-Jakob disease hit the newspapers' front pages. The molecular mechanisms responsible for the disease development are still not completely understood. Symptoms of prion diseases are dementia, motor system defects and amnesia. These symptoms are accompanied with neuropathological hallmarks in brain and the central nervous systems.

    However, previous observations presented a paradox: the molecular hallmarks have been found also in the absence of any prion disease symptoms. Vladimir Ermolayev, Rudolf Virchow Center, and colleagues of the Institute of Virology brought new insights in the understanding of the key factors triggering the onset of the clinical disease.

    Impaired axonal transport is known to be involved in the development of neurodegenerative diseases like Alzheimer's or Parkinson's. Previously, prion infections were shown to cause spongiform vacuolations, axonal swellings and accumulation of amyloid protein fibrils. The impaired axonal transport had not been observed so far.

    To monitor the axonal transport, Vladimir Ermolayev and co-authors injected special dyes into mouse motor neurons. These dyes attached to the transport system to be carried to the neuronal bodies. Combination of confocal and novel ultramicroscopy techniques enabled to monitor the dye delivery to the neurons and characterize the functional properties of axonal transport.

    After prion injection in brain and the motor neuron system, Ermolayev and colleagues observed the described clinical symptoms. When clinical symptoms occurred, the researchers found a clearly reduced axonal transport in the neurons of two brain centers, the red nucleus and the motor cortex. Axonal transport impairments were seen in 45 per cent of neurons in the red nucleus and up to 94 per cent of motor cortex neurons.

    "These results will help us to find better ways for diagnosis and treatment of prion diseases.", says Dr. Vladimir Ermolayev.

    Vladimir Ermolayev, Toni Cathomen, Julia Merk, Mike Friedrich, Wolfgang Härtig, Gregory S. Harms, Michael A. Klein, and Eckhard Flechsig: Impaired Axonal Transport in Motor Neurons correlates with Clinical Prion Disease, PLoS Pathogens 5(8): e1000558. doi:10.1371/journal.ppat.1000558


    Sonja Jülich-Abbas, Public Science Center, Rudolf Virchow Center/ DFG Research Center for Experimental Biomedicine, University of Würzburg, phone ++49 931 201 48714, sonja.juelich@virchow.uni-wuerzburg.de