The propagation of prion-like protein inclusions in neurodegenerative diseases.
The most common neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, are characterized by the misfolding of a small number of proteins that assemble into ordered aggregates in affected brain cells. For many years, the events leading to aggregate formation were believed to be entirely cell-autonomous, with protein misfolding occurring independently in many cells. Recent research has now shown that cell non-autonomous mechanisms are also important for the pathogenesis of neurodegenerative diseases with intracellular filamentous inclusions. The intercellular transfer of inclusions made of tau, alpha-synuclein, huntingtin and superoxide dismutase 1 has been demonstrated, revealing the existence of mechanisms reminiscent of those by which prions spread through the nervous system.
Goedert
Michel
M
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK. mg@mrc-lmb.cam.ac.uk
Clavaguera
Florence
F
Tolnay
Markus
M
D000818:Animals; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D011328:Prions; D016875:tau Proteins