Protein transmission in neurodegenerative disease.

1. Nat Rev Neurol. 2020 Apr;16(4):199-212. doi: 10.1038/s41582-020-0333-7. Epub 2020 Mar 23. Protein transmission in neurodegenerative disease. Peng C(1), Trojanowski JQ(2), Lee VM(3). Author information: (1)Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. (2)The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. (3)The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. vmylee@upenn.edu. Most neurodegenerative diseases are characterized by the intracellular or extracellular aggregation of misfolded proteins such as amyloid-β and tau in Alzheimer disease, α-synuclein in Parkinson disease, and TAR DNA-binding protein 43 in amyotrophic lateral sclerosis. Accumulating evidence from both human studies and disease models indicates that intercellular transmission and the subsequent templated amplification of these misfolded proteins are involved in the onset and progression of various neurodegenerative diseases. The misfolded proteins that are transferred between cells are referred to as 'pathological seeds'. Recent studies have made exciting progress in identifying the characteristics of different pathological seeds, particularly those isolated from diseased brains. Advances have also been made in our understanding of the molecular mechanisms that regulate the transmission process, and the influence of the host cell on the conformation and properties of pathological seeds. The aim of this Review is to summarize our current knowledge of the cell-to-cell transmission of pathological proteins and to identify key questions for future investigation. DOI: 10.1038/s41582-020-0333-7 PMCID: PMC9242841 PMID: 32203399 [Indexed for MEDLINE] Conflict of interest statement: Competing interests The authors declare no competing interests.