[Are neurodegenerative diseases "protein cancers"?].

In the last 30 years, the elucidation of the molecular pathogenesis of neurodegenerative diseases has undergone remarkable progress, including the discoveries of the causative genes and risk factors of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. However, the fundamental questions of why different neurons degenerate in different diseases and why these diseases are progressive have received little attention. I have proposed the "protein cancer" hypothesis, which states that abnormal or malignant proteins--such as prion proteins--generated in a cell grow and propagate from cell to cell by converting normal proteins, and this propagation causes disease progression, analogous to the metastasis of cancer cells to multiple different tissues during cancer progression. Intracellular filamentous inclusions composed of amyloid-like proteins, such as tau, α-synuclein, and TDP-43, are common neuropathological features of many neurodegenerative disorders, and the extent of the abnormal protein pathologies is closely related to disease progression. Recent results of experimental model studies as well as biochemical analyses of abnormal proteins in patients have provided support for this hypothesis. Therefore, small molecules or antibodies that can inhibit the intra- and intercellular propagation of abnormal proteins are expected to be promising candidates for clinical therapy.