Funded Studies
Study Rationale:The gap junctions that directly connect one cell with its neighbor have recently been implicated in the transfer of alpha-synuclein pathology associated with Parkinson’s disease (PD). Gap junction proteins called connexins are involved in establishing this intercellular con nectivity and promoting the transfer of molecules between cells. In neurodegenerative disorders such as PD, these proteins appear to be differentially regulated, altering cellular connectivity. Our aim is to target the neuronal connexins that are involved in the transfer of alpha-synuclein pathology between; blocking this cell-to-cell transmission could delay the onset of PD.
Hypothesis: This study aims to validate the role of the gap junction protein connexin-32 in the direct transfer of alpha-synuclein pathology between cells in a preclinical model of PD and to assess whether inhibiting this protein will reduce alpha-synuclein pathology.
Study Design: We recently identified the gap junction protein connexin-32 as being involved in the uptake and transfer of pathological forms of alpha-synuclein. Now, we will validate its role in alpha-synuclein transmission in a preclinical model of PD. This demonstration will allow us to validate the role of connexin-32 in animal models of PD and to test whether immunotherapeutic or pharmacological inhibition of connexin-32 will successfully block the transmission of alpha-synuclein pathology throughout the brain.
Impact on Diagnosis/Treatment of Parkinson’s disease: Confirmation that gap junction proteins are involved in the direct transfer of alpha-synuclein pathology will provide a novel therapeutic target that will allow us to design novel inhibitors that target these proteins and prevent the spread of pathology between cells.
Next Steps for Development: Given that gap junction inhibitors are currently in use for the treatment of unrelated disorders such as ulcers or seizures, we believe that novel inhibitors could be used as a complementary or alternative treatment to prevent the spread of alpha-synuclein pathology in PD and related disorders.