[Neurodegenerative disease and autophagy].
In neurodegenerative diseases, accumulation of aggregated proteins leads to inclusion body formation which is the hallmark of the pathological findings. Formation of inclusion bodies is now thought to be a cellular protective mechanism to collect aggregated proteins to a small compartment in the cell since more oligomeric form of aggregated proteins seem to have more toxicity than highly polymeric aggregates which are present in the inclusion bodies. The experimental inclusion body called aggresome is formed at microtubule organizing center by the help of microtubules and motor protein complex upon proteasome inhibition. Recently, the author reported that the collection of aggregated proteins to aggresome is closely related to their degradation by autophagy-lysosomal degradation system which strongly suggested that autophagy is a back-up system for ubiquitin proteasomal protein degradation system. Thus to find ways to upregulate protein degradation system including ubiquitin proteasome system and autophagy for therapeutic point of view is a quite promising strategy.
Iwata
Atsushi
A
Department of Neurology, University of Tokyo.
D001343:Autophagy / Q000502:physiology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000503:physiopathology*