Prion-like propagation of intracellular protein aggregates

Takashi Nonaka

Tokyo Metropolitan Institute of Medical Science, Dementia Research Project

The most common neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, are all protein-misfolding diseases, and are characterized by the presence of disease-specific protein aggregates in affected neuronal cells. Recent studies have shown that aggregation-prone proteins such as tau, alpha-synuclein and TDP-43 can form aggregates in a seed-dependent and self-templating prion-like manner in vitro and in vivo, suggesting that cell-cell transmission of aggregated proteins occurs in both cell culture and animal models. Therefore, it is thought that prion-like propagation of aberrant protein aggregates may be involved in the pathogenesis of neurodegenerative diseases.

Address correspondence to Dr. Takashi Nonaka, Tokyo Metropolitan Institute of Medical Science, Dementia Research Project (2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan)