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Repurposing gemfibrozil as a drug for the treatment of Alzheimer’s Disease


Project Description

An opportunity has arisen in the Division of Biomedical and Life Sciences (BLS) at Lancaster University for a talented researcher to investigate the possibility of repurposing an existing drug for the treatment of the world’s leading form of dementia, Alzheimer’s disease (AD). The post is fully funded including stipend, tuition fees and reagent costs (the latter largely funded by the ‘Defying Dementia’ campaign founded at the University; https://www.lancaster.ac.uk/defyingdementia/). You will be supported by an experienced and dedicated team of scientists; Dr. Ed Parkin, Dr. Chris Gaffney, Dr. Neil Dawson and Dr. Alex Benedetto who all excel in research areas relevant to the proposed PhD project (see https://www.lancaster.ac.uk/bls/people/ for further information).

Project specifics: AD may be caused by aberrant proteolysis of the amyloid-precursor-protein (APP) producing neurotoxic amyloid-beta (Abeta)-peptides [1]. The enzyme ADAM10 cleaves APP precluding Abeta-peptide formation leading, instead, to the formation of the neuroprotective fragment, sAPPalpha. ADAM10 also releases the prion protein, which binds Abeta-peptides and mediates their toxicity, from the surface of neurons. Therefore, enhancing ADAM10 activity in the brain represents a potential multi-mechanistic AD therapy [2]. Gemfibrozil, a drug currently used for cholesterol reduction, enhances cellular ADAM10 levels and traverses the blood-brain-barrier [3]. The current study will combine cell and in vivo (rodent and worm) models to investigate whether this drug can be repurposed for the treatment of AD.

Career benefits: You will develop broad expertise in a wide range of experimental methodologies including molecular biology, cell culture, immunohistochemistry, behavioural analysis and functional neuronal imaging in multiple systems. You will validate cell culture experiments in C. elegans and rodent models where the drug’s ability to protect cognition and brain function will be tested in a preclinical AD model. Given the importance of ADAM10 in other research areas including cancer, you will benefit from a range of future research employment possibilities. Furthermore, BLS provides extensive opportunities for professional development and has a highly supportive Divisional level support structure in place for post-graduate research students.

Feel free to contact any member of the supervisory team by email at , ; ; or for further details about the project and local facilities.

Applications are made by completing an application for PhD Biomedical and Life Sciences October 2019 through our online application system. Closing date: midnight 15th March 2019

Funding Notes

Awards are available for UK or EU students only for a maximum of three years full-time study. Awards will cover University Tuition Fees and stipend at Research Council Doctoral Stipend Level (2018-2019: £14,777).

References

1. Andrew, R.J., et al., A Greek Tragedy: The Growing Complexity of Alzheimer Amyloid Precursor Protein Proteolysis. J Biol Chem, 2016. 291(37): p. 19235-44.

2. Peron, R., et al., Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment. Pharmaceuticals (Basel), 2018. 11(1).

3. Corbett, G.T., F.J. Gonzalez, and K. Pahan, Activation of peroxisome proliferator-activated receptor alpha stimulates ADAM10-mediated proteolysis of APP. Proc Natl Acad Sci U S A, 2015. 112(27): p. 8445-50.

How good is research at Lancaster University in Allied Health Professions, Dentistry, Nursing and Pharmacy?

FTE Category A staff submitted: 64.40

Research output data provided by the Research Excellence Framework (REF)

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