title: Protein aggregate spreading in neurodegenerative diseases: problems and perspectives.
abstract: Progressive accumulation of specific protein aggregates is a defining feature of many major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, fronto-temporal dementia, Huntington's disease, and Creutzfeldt-Jakob disease (CJD). Findings from several recent studies have suggested that aggregation-prone proteins, such as tau, α-synuclein, polyglutamine-containing proteins, and amyloid-β, can spread to other cells and brain regions, a phenomenon considered unique to prion disorders, such as CJD and bovine spongiform encephalopathy. Cell-to-cell propagation of protein aggregates may be the general underlying principle for progressive deterioration of neurodegenerative diseases. This may also have significant implications in cell replacement therapies, as evidenced by the propagation of α-synuclein aggregates from host to grafted cells in long-term transplants in Parkinson's patients. Here, we review recent progress in protein aggregate propagation in experimental model systems and discuss outstanding questions and future perspectives. Understanding the mechanisms of this pathological spreading may open the way to unique opportunities for development of diagnostic techniques and novel therapies for protein misfolding-associated neurodegenerative diseases.
authors.affiliation: Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea. sjlee@konkuk.ac.kr
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hee-Sun
authors.initials: HS
authors.lastname: Lim
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: He-Jin
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology*; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000378:metabolism / Q000473:pathology
chemical_list: D009419:Nerve Tissue Proteins