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Alpha-synuclein-Binding Proteins on the Cell Surface as Novel Therapeutic Targets

Study Rationale:
Alpha-synuclein is a sticky protein that clumps in the brains of people with Parkinson's disease (PD). Recent research suggests that clumps of alpha-synuclein spreads in the brain from cell to cell, driving disease progression. Exactly how alpha-synuclein clumps bind and enter cells is still unclear. The aim of this study is to identify proteins on the surface of the cell that recognize alpha-synuclein clumps and allow them to stick to the cell to determine a potential role of these proteins in PD.

We hypothesize that toxic clumps of alpha-synuclein are recognized by some proteins on the cell surface, and that those proteins mediate the toxic effect of alpha-synuclein and/or contribute to its spread in the brain.

Study Design:
We have performed a thorough search for proteins on the cell surface that recognize toxic alpha-synuclein clumps. The search included more than 4,000 proteins, approximately 85% of all proteins located on the surface of the cell. We have identified nine novel proteins that strongly bind toxic alpha-synuclein clumps. Now we aim to examine their potential role in Parkinson's.

Impact on Diagnosis/Treatment of Parkinson's Disease:
To stop disease progression, we need to understanding how alpha-synuclein clumps spread and exert their toxic effect in the brain. This study has identified novel cell-surface proteins that bind alpha-synuclein and could be potential targets for therapeutics designed to slow Parkinson's progression.

Next Steps for Development:
Disrupting or preventing the interaction of alpha-synuclein clumps with the surface of the cell is a potential strategy to stop the spread of alpha-synuclein or avoid its toxic effects. This can be accomplished via several therapeutic approaches, such as antibodies or pharmaceuticals.


  • Stephen M. Strittmatter, MD, PhD

    New Haven, CT United States

  • Azucena Perez-Canamas, PhD

    New Haven, CT United States

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