Prion Diseases Transmissible Spongiform Encephalopathies

Animal Prion Diseases Human Prion Diseases

Prion diseases, a group of fatal neurodegenerative diseases affecting both humans and animals, are unique in that they can be both infectious (transmissible) and heritable. The causative pathogen is a proteinaceous infectious agent termed prion protein (PrPsc) (sc refers to scrapie). PrPsc is a protease-resistant isoform of a cellular prion protein (PrPc) (c refers to cellular) that is normally folded in the membranes of the neurons and glial cells of the central nervous system (CNS). PrPsc also is present in the lymphoreticu-lar system, heart, and skeletal muscles. The gene of the human prion protein (PRNP) is located on the short arm of chromosome 20. PRNP is polymorphic at codon 129, encoding either for valine or methionine. The non-pathogenic PrPc, by changing the folding pattern, can convert to a pathogenic PrPsc spontaneously or by pathogenic mutations in PRNP. The PrPsc is unique in several respects: It consists solely of protein and lacks nucleic acid, it resists conventional sterilizing agents, it evokes neither inflammatory nor immune reaction, and it does not form neuronal inclusions. Due to its high infectivity, guidelines have been established for the handling of specimens from patients suspected of having a prion disease. By inoculation or ingestion, PrPsc is transmissible from animal to animal, from human to experimental animals, from human to human, and evidence exists for transmission from animal to human.

The characteristic pathologic feature shared by both human and animal diseases is a spongiform degeneration of the cerebral and cerebellar cortex and deep gray structures. Hence the name, transmissible spongiform encephalopathy.

Recent experimental studies raised the possibility of a role for Spiroplasma infection in the development of transmissible spongiform encephalopathies. Spiro-plasma, an intracellular, highly infective, neurotropic bacteria spread by the oral route, reaches the neural tissue from the lymphatics. A possible interaction with prion proteins and a possible role in causing spongiform encephalopathies awaits elucidation.

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