The ubiquitin-proteasome system in Alzheimer's disease

* • Introduction * • Biology of the UPS- The tagging reaction- Structure of the proteasome * • The involvement of the UPS in AD pathogenesis- The interaction between Aβ and the proteasome- The interaction between the UPS and tau * • The UPS as a link between Aβ and tau interaction * • Conclusions Abstract Accumulation of proteins is a recurring event in many neurodegenerative diseases, including Alzheimer's disease (AD).Evidence has suggested that protein accumulation may result from a dysfunction in the ubiquitin proteasome system (UPS). Indeed, there is clear genetic and biochemical evidence of an involvement of the ubiquitin proteasome system in AD. This review summarizes the data supporting an involvement of the UPS in the pathogenesis of AD, focusing on the data showing the relationship between Aβ and tau, the two hallmark lesions of AD, and the UPS.