Dr Edward Parkin is interested in the role played by the proteolysis of cell proteins in neurodegenerative conditions such as Alzheimer's disease and cancers, particularly prostate cancer. 

The amyloid precursor protein (APP), Alzheimer's disease and gene therapy

Alzheimer's disease (AD) is a neurodegenerative condition caused by accumulation within the brain of neurotoxic amyloid beta (Aß)-peptides. These short peptides are derived from the larger amyloid precursor protein (APP) through sequential cleavage by two enzymes known as β- and γ-secretases. Alternatively, APP can be shed from the cell surface through the action of an α-secretase which cleaves within the Aß region of the molecule thereby precluding the formation of intact Aß-peptides. We are particularly interested in the role played by a group of enzymes called 'ADAMs' in α-secretase cleavage of APP. Up-regulation of these enzyme activities may be beneficial in AD. We are very interested in soluble extracellular APP fragments such as sAPPα which has beneficial properties for neurons. As such we are also interested in developing gene therapy methods to specifically enhance the production of this and other protective proteins by neurons.

APP and cancer

Although APP has received most attention for its role in AD, more recent studies, including our own, have shown that the protein has a role to play in various cancers. We have shown that copper binding by this protein enables prostate cancer cells to grow effectively despite the high concentrations of this metal found in tumours. We have also shown that APP induces a change in prostate cancer cells known as epithelial-to-mesenchymal transition (EMT) which facilitates spread of the cancer throughout the body.

Notch signalling in cancer

Notch signalling is a mechanism that cells use to communicate with each other, essentially telling each other how to grow and divide. When this signalling pathway breaks down the cells grow uncontrollably into tumours. We are very interested in the role played by Notch signalling in prostate and colorectal cancers.