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Volume 08
Journal of Alzheimers Disease & Parkinsonism
Alzheimer's Congress 2018
May 30-31, 2018
May 30-31, 2018 Osaka, Japan
10
th
World Congress on
Alzheimer's Disease & Dementia
Rab21, a novel PS1 interactor, regulates γ-secretase activity via PS1 subcellular distribution
Hong Qing
Beijing Institute of Technology, China
T
he γ-secretase has been a therapeutically target for its key role in cleaving APP to generate β-Amyloid (Aβ), the primary
constituents of senile plaques and a hallmark of Alzheimer’s Disease (AD) pathology. Recently, γ-secretase associating
proteins showed promising role in specifically modulating APP processing while sparing Notch signaling; however, the
underlying mechanism is still unclear. A Co-Immunoprecipitation (Co-IP) coupled with mass spectrometry proteomic assay
for Presenilin1 (PS1, the catalytic subunit of γ-secretase) was firstly conducted to find more γ-secretase associating proteins.
Gene ontology analysis of these results identified Rab21 as a potential PS1 interacting protein, and the interaction between
them was validated by reciprocal Co-IP and immunofluorescence assay. Then, molecular and biochemical methods were used
to investigate the effect of Rab21 on APP processing. Results showed that overexpression of Rab21 enhanced Aβ generation,
while silencing of Rab21 reduced the accumulation of Aβ, which resulted due to change in γ- secretase activity rather than α- or
β-secretase. Finally, we demonstrated that Rab21 had no effect on γ-secretase complex synthesis or metabolism but enhanced
PS1 endocytosis and translocation to late endosome/lysosome. In conclusion, we identified a novel γ-secretase-associating
protein Rab21 and illustrate that Rab21 promotes γ-secretase internalization and translocation to late endosome/lysosome.
Moreover, silencing of Rab21 decreases the γ-secretase activity in APP processing thus production of Aβ. All these results open
new gateways towards the understanding of γ-secretase-associating proteins in APP processing and make inhibition of Rab21
a promising strategy for AD therapy.
hqing@bit.edu.cnJ Alzheimers Dis Parkinsonism 2018, Volume 8
DOI: 10.4172/2161-0460-C4-046