Direct cellular connectivity has recently been implicated in the transfer of alpha-synuclein pathology associated with Parkinson’s disease. The gap junction proteins known as connexins are involved in promoting connectivity between cells. They promote the transfer of molecules between cells to monitor the surrounding environment. In brain disorders these proteins appear to be differentially regulated thereby increasing or decreasing cellular connectivity. Our aim is to target neuronal connexins particularly involved in the transfer of alpha-synuclein pathology between cells to block this transmission and delay the onset of Parkinson’s disease.
Our aim is to validate targeting the gap junction protein connexin-32 as a novel therapeutic strategy to prevent or delay the onset of Parkinson’s disease.
We will validate the role of connexin-32 in alpha-synuclein transmission in a pre-clinical model of Parkinson’s disease. This will allow us to test whether immunotherapy or pharmacological inhibition of connexin-32 successfully blocks the transmission of alpha-synuclein pathology throughout the brain.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
The identification of gap junction proteins involved in the direct transfer of alpha-synuclein pathology will provide a novel therapeutic strategy that will allow the design of novel inhibitors to target these proteins and prevent the spreading 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 designer inhibitors could be used as a complementary or alternative treatment to prevent the spreading of alpha-synuclein pathology in Parkinson’s disease and related disorders.