Small ubiquitin-like modifiers (SUMO) are covalently conjugated to target proteins and modulate a growing number of cellular pathways. SUMOs have been strong links to tumorgenesis and metastasis due to regulation of nuclear events. More recently, increasing evidence has demonstrated their role in neuronal pathways such as synaptic plasticity and memory as well as several neurodegenerative diseases.
In the current study, we examines the impact of SUMO1 on processing of the amyloid precursor protein (APP)　leading to the production and deposition of the amyloid beta (Aβ) peptide. An in vivo model of these pathways was developed by the generation of double transgenic mice over-expressing human SUMO1 and a mutant APP. The SUMO1-APP transgenics exhibited increased insoluble Aβ and plaque density accompanied by increased dendritic spine loss, more pronounced synaptic and cognitive deficits at later ages. Then we examined several possible mechanisms for the SUMO1-mediated increase in amyloid load.
In this presentation, we will show our results and explain the possible involvement of SUMO1 in the pathology of AD.