Those diseases are caused by the conversion of a host-derived cellular prion protein to the infectious scrapie prion protein , a misfolded and proteinase K -resistant isoform, which represents the major component of infectious agent in brains. Although it is clear that PrPSc accumulates in the brain during most prion diseases, there is uncertainty about the mechanisms responsible for neuronal death. Usually, PrPC is anchored on the cell surface via a GPI moiety and begins its journey to the cell surface in endoplasmic reticulum. However, some PrP molecules are not co-translationally inserted into the ER and end up in the cytosol. Cytosolic PrP accounts for a minor intracellular subset of PrPC that has attracted much attention because its accumulation sensitizes cell to death. Recent study proposes the evidence that cytosolic PrP is neurotoxic and may play a role in the neurodegeneration of prion disease.. Cytosolic PrP, either from retro-translocation or from the impaired import into the ER , is destined for proteasome degradation. Moreover, changes of the normal secreting and maturing pathway of wild-type PrP will cause Temozolomide obvious cytotoxic activity in the cultured cells, possibly due to the generation of intracellular PrP. The accumulation of PrP in the cytosol may trigger cell apoptosis by mitochondrial relative apoptosis pathway. PrP shows characteristics to interact with microtubular cytoskeleton and its major component, tubulin. Microtubules are cellular structures that play a central role in intracellular transport, metabolism, and cell division. Interference with microtubule dynamics leads to mitotic arrest and initiation of apoptosis. Our previous studies have also confirmed that the expressed cytosolic PrP is able to interact with endogenous tubulin, and that accumulation of cytosolic PrP apparently disrupts the microtubule network in the cultured cells and reduces the cell viability via inducing apoptosis. TPPP/p25 is a recently discovered, brain-specific unstructured protein involved in brain function. It is found predominantly in oligodendrocytes in normal brain but is enriched in neuronal and glial WZ4002 inclusions of Parkinson��s disease and other synucleinopathies. Its physiological function seems to be the dynamic stabilization of microtubular ultrastructures, as well as the projections of mature oligodendrocytes and ciliary structures. Microtubules, which form a major part of the cytoskeleton, display many physiological functions in eukaryotic cells. The dynamic reorganizing ability and stability of microtubular systems show great variability in different tissues and at different stages of tissue development.