Therapies for human prion diseases

[摘要] The pathological foundation of human prion diseases is a result of the conversion of the physiological form of prion protein (PrP^c) to the pathological protease resistance form PrP^res. Most patients with prion disease have unknown reasons for this conversion and the subsequent development of a devastating neurodegenerative disorder. The conversion of PrP^c to PrP^res, with resultant propagation and accumulation results in neuronal death and amyloidogenesis. However, with increasing understanding of neurodegenerative processes it appears that protein-misfolding and subsequent propagation of these rouge proteins, is a generic phenomenon shared with diseases caused by tau, α-synucleins and β-amyloid proteins. Consequently, effective anti-prion agents may have wider implications. A number of therapeutic approaches include polyanionic, polycyclic drugs such as pentosan polysulfate (PPS), which prevent the conversion of PrP^c to PrP^res and might also sequester and down-regulate PrP^res. Polyanionic compounds might also help to clear PrP^res. Treatments aimed at the laminin receptor, which is an important accessory molecule in the conversion of PrP^c to PrP^res – neuroprotection, immunotherapy, siRNA and antisense approaches have provided some experimental promise.

[学科分类] 精神健康和精神病学

[关键词] Prion diseases;Creutzfeldt-Jakob disease;treatments;neurodegenerative diseases;protein misfolding;protein propagation