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Funded Studies

Evaluation of LRRK2-derived Bioportides as Functional Protein Modulators and Potential Therapeutics

The therapeutic actions of most existing drugs are the result of their binding to molecules known as proteins that are associated with certain cells of the human body. However, many proteins exist only within cells, and many drugs cannot pass through cell walls. More recently, a new type of agent called cell penetrating peptides (CPPs), have been identified that penetrates cells very efficiently. We will identify innovative CPPs with the objective of producing both research tools and improved treatment options for Parkinson’s disease.

Project Description: 
A protein known as LRRK2 is very likely to represent a new drug target for Parkinson’s disease. Understanding the function of this protein and the development of new technologies to target LRRK2 are fundamental to the design of improved treatment options. We can predict that smaller fragments of LRRK2, molecules known as peptides, will be able to enter diseased cells and interact very specifically with LRRK2. Our objectives are, therefore, to identify one or more of these peptides that can be used to either improve the delivery of existing drugs or to directly change the distribution and/or function of the LRRK2 protein. To do this we will determine the uptake of peptide into cells, their ability to specifically bind to LRRK2 and their influence on protein function. Ultimately, we hope to identify a new molecule that offers promise for the development of a new treatment option for Parkinson’s disease.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:  
The protein LRRK2 is a large and very complex molecule that is only now becoming understood in detail. However, it is recognized that subtle changes in the structure of LRRK2 can lead to Parkinson’s disease in some patients. Thus, agents that can influence either the distribution or function of LRRK2 within cells offer enormous promise to further understand the normal function of the protein and to elucidate how subtle changes contribute to Parkinson’s disease. We anticipate that our project will provide a range of innovative research tools to probe the many predicted functions of LRRK2. We also hope to identify candidate molecules that can be further developed to provide useful therapeutic action.

Anticipated Outcome:
We can predict that small fragments of LRRK2 may be therapeutically useful. Our biological assays will select such molecules that can very effectively enter into cells where the LRRK2 protein is located. Further tests will positively identify some molecules that can also influence the biological functions of LRRK2. Thus, on completion of this project we will have developed innovative research tools and putative therapeutic agents. The employment of such molecules will enhance our currently limited understanding of LRRK2 and illuminate new treatment modalities.


  • John Howl, PhD

    Wolverhampton United Kingdom

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