Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases

• Published in: Nature medicine Vol. 20; no. 2; pp. 130 - 138
• Main Authors: Guo, Jing L, Lee, Virginia M Y
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2014; Nature Publishing Group
• Subjects: 631/378/1689/364; 692/699/375/365; Aggregates; Amyloidogenic Proteins - classification; Amyloidogenic Proteins - metabolism; Biomedicine; Cancer Research; Cell Communication - physiology; Cell interaction; Cellular biology; Degeneration; Glycoproteins; Heterogeneity; Humans; Identification and classification; Infectious Diseases; Medical research; Medicine, Experimental; Metabolic Diseases; Models, Biological; Molecular Medicine; Nervous system; Neurodegenerative Diseases - physiopathology; Neurological disorders; Neuropathology; Neurosciences; Pharmacology; Protein Transport - physiology; Proteins; Proteostasis Deficiencies - physiopathology; review-article
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/nm.3457

Numerous neurodegenerative diseases show deposition of protein aggregates, which are thought to cause neuronal damage. This Review discusses how cell-to-cell transmission of these pathogenic misfolded proteins is involved in initiation and progression of the disease and examines the clinical relevance of different strains in the heterogeneity of neurodegenerative disorders. A common feature of many neurodegenerative diseases is the deposition of β-sheet-rich amyloid aggregates formed by proteins specific to these diseases. These protein aggregates are thought to cause neuronal dysfunction, directly or indirectly. Recent studies have strongly implicated cell-to-cell transmission of misfolded proteins as a common mechanism for the onset and progression of various neurodegenerative disorders. Emerging evidence also suggests the presence of conformationally diverse 'strains' of each type of disease protein, which may be another shared feature of amyloid aggregates, accounting for the tremendous heterogeneity within each type of neurodegenerative disease. Although there are many more questions to be answered, these studies have opened up new avenues for therapeutic interventions in neurodegenerative disorders.