Cellular and Molecular Mechanisms of Prion Disease

Annu Rev Pathol. 2019 Jan 24;14:497-516. doi: 10.1146/annurev-pathmechdis-012418-013109. Epub 2018 Oct 24.

Abstract

Prion diseases are rapidly progressive, incurable neurodegenerative disorders caused by misfolded, aggregated proteins known as prions, which are uniquely infectious. Remarkably, these infectious proteins have been responsible for widespread disease epidemics, including kuru in humans, bovine spongiform encephalopathy in cattle, and chronic wasting disease in cervids, the latter of which has spread across North America and recently appeared in Norway and Finland. The hallmark histopathological features include widespread spongiform encephalopathy, neuronal loss, gliosis, and deposits of variably sized aggregated prion protein, ranging from small, soluble oligomers to long, thin, unbranched fibrils, depending on the disease. Here, we explore recent advances in prion disease research, from the function of the cellular prion protein to the dysfunction triggering neurotoxicity, as well as mechanisms underlying prion spread between cells. We also highlight key findings that have revealed new therapeutic targets and consider unanswered questions for future research.

Keywords: amyloid; neurodegeneration; neurotoxicity; prion transmission; strains.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyloid
  • Animals
  • Cattle
  • Deer
  • Humans
  • Neurodegenerative Diseases
  • Prion Diseases / etiology
  • Prion Diseases / metabolism
  • Prion Diseases / physiopathology*
  • Prion Diseases / transmission
  • Prion Proteins / metabolism*
  • Prion Proteins / physiology

Substances

  • Amyloid
  • Prion Proteins