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Prion protein (PrPC) was originally known as the causative agent of transmissible spongiform encephalopathy (TSE) but with recent research, its true function in cells is becoming clearer. It is known to act as a scaffolding protein, binding multiple ligands at the cell membrane and to be involved in signal transduction, passing information from the extracellular matrix (ECM) to the cytoplasm. Its role in the coordination of transmitters at the synapse, glyapse, and gap junction and in short- and long-range neurotrophic signaling gives PrPC a major part in neural transmission and nervous system signaling. It acts to regulate cellular function in multiple targets through its role as a controller of redox status and calcium ion flux. Given the importance of PrPC in cell physiology, this review considers its potential role in disease apart from TSE. The putative functions of PrPC point to involvement in neurodegenerative disease, neuropathic pain, chronic headache, and inflammatory disease including neuroinflammatory disease of the nervous system. Potential targets for the treatment of disease influenced by PrPC are discussed.
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