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Amyloid fibrils of mammalian prion protein induce axonal degeneration in NTERA2‐derived terminally differentiated neurons
Author(s) -
Novitskaya Vera,
Makarava Natallia,
Sylvester Ian,
Bronstein Igor B.,
Baskakov Ilia V.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04537.x
Subject(s) - synaptophysin , fibril , biology , gene isoform , microtubule , microbiology and biotechnology , synapse , neuroscience , senile plaques , degeneration (medical) , pathogenesis , tau protein , subcellular localization , alzheimer's disease , pathology , cytoplasm , immunohistochemistry , biochemistry , disease , immunology , medicine , gene
Defects in axonal transport and synaptic dysfunctions are associated with early stages of several neurodegenerative diseases including Alzheimer’s, Huntington’s, Parkinson’s, and prion diseases. Here, we tested the effect of full‐length mammalian prion protein (rPrP) converted into three conformationally different isoforms to induce pathological changes regarded as early subcellular hallmarks of prion disease. We employed human embryonal teratocarcinoma NTERA2 cells (NT2) that were terminally differentiated into neuronal and glial cells and co‐cultured together. We found that rPrP fibrils but not α‐rPrP or soluble β‐sheet rich oligomers caused degeneration of neuronal processes. Degeneration of processes was accompanied by a collapse of microtubules and aggregation of cytoskeletal proteins, formation of neuritic beads, and a dramatic change in localization of synaptophysin. Our studies demonstrated the utility of NT2 cells as valuable human model system for elucidating subcellular events of prion pathogenesis, and supported the emerging hypothesis that defects in neuronal transport and synaptic abnormalities are early pathological hallmarks associated with prion diseases.