Prion-like propagation of abnormal proteins in neurodegenerative diseases

Masato Hasegawa

Department of Dementia and Higher Brain Function, Tokyo Metropolytan Institute of Medical Science

Progressive neurodegeneration with accumulation of abnormal protein deposits is a common neuropathological feature of many neurodegenerative diseases, such as Alzheimer's disease, Parkinson disease and amyotrophic lateral sclerosis. However, it remains unknown why these diseases are progressive and why the same pathologies spread to different brain regions. Prion-like propagation or spreading of intracellular abnormal proteins, such as tau, alpha-synuclein or TDP-43 is hypothesized to account for this “progressive” neurodegenerative disorders.
Neuropathological and biochemical studies of autopsy cases as well as experimental data using cellular and animal models strongly support this hypothesis. This concept has important implications for the design of disease-modifying drugs or therapies to regulate the progression of diseases.

Address correspondence to Masato Hasegawa, Department of Dementia and Higher Brain Function, Tokyo Metropolytan Institute of Medical Science (2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan)