Role of mTORC1 signalling in intracellular processing and trafficking of Alzheimer’s diseaseassociated amyloid precursor protein and its derivatives

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Alzheimer’s disease (AD) is the most frequent neurodegenerative disease and might result in personality changes. Deposition of extracellular amyloid (Aβ) plaques is the main molecular symptom of AD, where Aβ is a product of the intracellular proteolysis of amyloid precursor protein (APP). mTORC1 is a key intracellular signalling component and its hyperactivity has been demonstrated in AD mice but also in post mortem human AD brains. In this proposal we focus on the link between mTORC1 and APP processing in SH-SY5Y neuroblastoma cells. We plan to modulate mTORC1 activity and correlate it with APP processing and Aβ oligomerization. Super-resolution fluorescence microscopy will localize and quantify APP, its derivatives and mTORC1. Cholesterol molecules have been shown to be important molecules in AD pathology. We aim to investigate the impact of cholesterol on the APP processing and mTORC1 signalling. We believe that new information about the interplay between the lipids, mTORC1 signalling and APP processing might be an important aspect in the treatment of AD.

Mgr. ŠTEFL Martin Ph.D.