Personnel

Dr Hilary McMahon BSc PhD

• Position:Lecturer, School of Biomolecular and Biomed Science; Conway Fellow, Conway Institute of Biomolecular & Biomedical Research
• Contact details: Health Sciences Centre, Belfield, Dublin 4
• Email: hilary.mcmahon@ucd.ie
• Telephone: 353-01-7166689

Research Interests

Prion diseases also known as Transmissible Spongiform Encephalopathies (TSEs) are a group of neurodegenerative disorders affecting animals and humans.  They are generally associated with the accumulation in the brain of an abnormal partially protease resistant isoform (PrPSc) of the normal endogenous prion protein (PrPC). The exact function of PrPC is not known, however most recent evidence indicates that this evolutionarily conserved protein has a role not only in TSEs but also in Alzheimer's disease (AD).

Dr. McMahon's group studies the biochemical basis of prion diseases, potential prion therapeutics and the link between AD and prion disorder. 

Links between the prion protein and Alzheimer's disease (AD). In AD abnormal processing of the amyloid precursor protein (APP) yielding amyloid beta (Aß) peptides is linked with the disease process. PrPC is now thought to play a role in AD because: The presence of PrPC has been shown to regulate Aß peptide production.  In the brains of TSE infected animals, where PrPC is converted to PrPSc, Aß levels are elevated. Mutant PrP associated with familial TSEs loose their ability to reduce Aß production.  This finding highlights the potential risk of developing additional complications in TSEs, and the severity of disease that could emanate from sporadic or infectious TSE in a patient with familial AD. AD diagnosis has already been made in disease cases arising from mutations resulting in expression of amino truncated PrPC.  These cases resulted from stop mutations in PRNP (the prion protein gene), which led to a form of PrPC that could not be transported to the cell surface. Adding to the link between PrPC and APP processing is the Valine/Methionine polymorphism at position 129 on PRNP, which has been identified as a risk factor in early onset AD.

• The biochemical mechanisms behind Prion diseases
• Therapeutic approaches to treat these disorders
• The link between Prion disorders and Alzheimer's disease   

Publications

Molloy B, McMahon HE. (2013) 'A cell biased effect of estrogen in prion infection'.J Virol. 88(2):1342-53

McMahon HEM (2012) 'Prion processing: a double-edged sword?'. Biochemical Society Transactions, 40 (4):735-738

McEvoy K. and McMahon H.E.M. ; (2009) 'Antiprion action of new cyclodextrin analogues'. Biochimica et Biophysica Acta, 1790 (10):1382-1386.

Soler L., Caffrey P. and McMahon H.E.M.; (2008) 'Effects of new amphotericin analogues on the scrapie isoform of the prion protein'. Biochimica Et Biophysica Acta, 1780 (10):1162-1167.

Prior, M., Lehmann, S., Sy, MS., Molloy, B., McMahon, H.E.; (2007) 'Cyclodextrins inhibit replication of scrapie prion protein in cell culture'. Journal of Virology, 81 (20):11195-11207.

Research Funding

Relevant Links

http://www.ucd.ie/conway/research/researchers/conwayfellowsa-z/drhilarymcmahon/

http://www.ucd.ie/sbbs/sbbsstaff/academicstaff/hmcmahon/