Cell-to-cell transmission of non-prion protein aggregates.
Neurodegenerative disorders such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and Creutzfeldt-Jakob disease (CJD) are characterized by progressive accumulation of protein aggregates in selected brain regions. Protein misfolding and templated assembly into aggregates might result from an imbalance between protein synthesis, aggregation and clearance. Although protein misfolding and aggregation occur in most neurodegenerative disorders, the concept of spreading and infectivity of aggregates in the CNS has, until now, been confined to prion diseases such as CJD and bovine spongiform encephalopathy. Emerging evidence, however, suggests that prion-like spreading, involving secreted proteins such as amyloid-β and cytosolic proteins such as tau, huntingtin and α-synuclein, can occur in other neurodegenerative disorders. The underlying molecular mechanisms and the therapeutic implications of the new data are discussed in this article.
Department of Biomedical Science and Technology, Konkuk University, 1 Hwayangdong, Gwangjin-gu, Seoul, Korea.
Seung-Jae
SJ
Lee
Paula
P
Desplats
Christina
C
Sigurdson
Igor
I
Tsigelny
Eliezer
E
Masliah
D000818:Animals; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D058225:Plaque, Amyloid / Q000209:etiology / Q000378:metabolism / Q000473:pathology
D009419:Nerve Tissue Proteins