Takashi Momoi Pages 111 - 118 ( 8 )
The expanded polyglutamine (polyQ) tracts observed in autosomal dominant neurodegenerative disorders have the tendency to form intracellular aggregates, thus enhancing apoptotic cell death and the formation of autophagic vesicles. PolyQ accumulation inhibits the ERassociated degradation system (ERAD) resulting in reduced retrotranslocation from the ER and increased accumulation of misfolded proteins in the lumen of ER. Autophagy is an early cellular defense mechanism associated with ER stress, but prolonged ER stress may induce autophagic cell death, with destruction of cellular components and apoptotic cell death. Endoplasmic reticulum (ER) stress may be the key signal for both of these events.
microtubles, proapoptotic Bcl-2 family, Caspase-12, polyQ aggregation, preautophagosomal membrane
Divisions of Development and Differentiation, Inherited Metabolic Disorders, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi-machi, Kodaira, Tokyo 187-8502, Japan.