Using advanced cell culture and proteomics (the study of the proteins of a cell), Lauren Richardson from Nottingham Trent University will be researching Parkinson’s disease. This will help to replace the use of primates, rats or mice.

SUPERVISOR: Dr Luigi De Girolamo - Nottingham Trent University

STUDENT: Miss Lauren Richardson

Parkinson’s disease (PD) is a complex and debilitating disorder that affects more than 127,000 people in the UK. It is a consequence of the progressive death of specific brain cells within the brain region that controls movement. What causes these brain cells to die is not known but is linked to the impairment of a number of biological processes. Unfortunately, to improve the understanding of these processes investigators use animal experimentation to recreate the biological impairment in the brain and test the potential of new drugs to alleviate the disease.

Currently, PD is diagnosed by clinical criteria and is only confirmed after a patient‘s death. Medical improvements could be achieved by identifying biological factors (proteins) that allow the identification of individuals at risk, the monitoring of disease progression and the response to drug treatment. The use of a human cell model that mimics the cells lost in PD would provide a platform to investigate the disease process and new drug compounds reducing the need for animals. We propose to use human cell models and chemical inhibitors to recreate the biological impairments that are known to be altered in PD brains to mimic the disease process. By collecting the proteins that are secreted by these degenerating cells and applying a powerful analytical approach, we will identify target proteins that represent a “biological fingerprint” of the disease. A comparison of the biological fingerprints with those identified from patient samples will provide a valuable tool to assess the effectiveness of new drug compounds.

Historically, a number of animal models (namely rodents and non-human primates) have been used to investigate mechanism of Parkinson's disease (PD) and neuroprotective strategies. The former are generally based on either genetic mutation of PD-related genes whilst the latter involve the induction of PD-like symptoms by exposure to chemical inhibitors. However, these models have significant limitations including the absence of specific clinical features, differences in pathology of specific brain areas, the absence of specific cell pathology and none faithfully recreate the complex chronic neurodegenerative timeframe of human PD (1).

REFERENCES: (1) Blesa J, Przedborski S. (2014). Parkinson’s disease: animal models and dopaminergic cell vulnerability. Frontiers in Neuroanatomy 155: 1-12; (2) Duty S, Jenner P. (2011) Animal models of Parkinson’s disease: a source of novel treatments and clues to the cause of the disease. British Journal of Pharmacology. 164(4):1357-1391.; (3) Sowell RA, Owen JB, Butterfield DA (2009). Proteomics in animal models of Alzheimer's and Parkinson's diseases. Ageing Res Rev. 8(1):1-17.