Mechanisms of intracellular aberrant protein aggregation and its regulation

Takashi Nonaka, Masato Hasegawa

Department of Neuropathology and Cell Biology, Dementia Research Project, Tokyo Metropolitan Institute of Medical Science

Recently, the propagation hypothesis of prion-like protein inclusions in neurodegenerative diseases has been focused. Many experimental results support that intracellular aggregates of tau, alpha-synuclein or huntingtin could be transferred intercellularly to neighbor cells and seeded for aggregation of each soluble protein. Propagation of aggregated proteins in these diseases may therefore occur through mechanisms similar to those that underlie prion pathogenesis. If this hypothesis is verified in vivo, it will suggest new therapeutic strategies to block propagation of aggregated proteins throughout the brain.

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