Objective/Rationale:
Mutations in an enzyme known as PINK1 can cause Parkinson’s disease. There has been
great interest in understanding the function of PINK1 since uncovering the pathways that
PINK1 is involved in may advance knowledge on the mechanisms of cell death in
Parkinson’s disease. We recently found that PINK1 targets another enzyme called parkin
which is also mutated in Parkinson’s disease patients. Our initial studies provide a
platform for more detailed studies into the PINK1-parkin pathway. This proposal
involves generation of reagents termed monoclonal antibodies that should help the
research community uncover greater information on the PINK1-parkin pathway. This
may ultimately lead to greater understanding into the cellular pathways that control cell
survival in Parkinson’s disease.
Project Description:
This project involves working closely with the MJFF and a company (Epitomics) to raise
state of the art pre-clinical monoclonal antibodies that detect phosphorylated Ser65-parkin and
phosphorylated Thr257-PINK1. Our laboratory will provide Epitomics with the key
phosphopeptide antigens to raise the antibodies against. Our lab will then evaluate the
quality of the antibodies that are raised in various applications including immunoblot. We
will select the optimal antibodies for each application and ensure that these are
distributed with no strings attached to the scientific community working on PINK1 and
parkin and Parkinson’s disease. We will also characterize two monoclonal antibodies
being raised by MJFF in collaboration with Epitomics and Neuromab against the total
PINK1 protein.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
We hope that the phospho-Ser65 parkin; phospho-Thr257 PINK1; and total PINK1
antibodies will be useful to researchers as well as pharmaceutical companies who are
studying PINK1 and parkin. We speculate that utilizing these phospho-specific antibodies
to monitor the PINK1-parkin pathway may have a diagnostic role as potential biomarkers
that could impact clinically on how we evaluate and monitor Parkinson’s disease
progression. This could be valuable to clinicians and pharmaceutical companies currently
involved in therapeutic trials in Parkinson’s disease.
Anticipated Outcome:
We aim to produce state of the art antibody reagents that will help with the
characterization and understanding of the PINK1-parkin pathway. These reagents will
greatly facilitate the ability of researchers and pharmaceutical companies to better
understand PINK1 and parkin biology and provide a framework on which there can be
greater understanding into the cellular networks that are crucial for cell survival in
Parkinson’s disease.