Protein aggregates of varying sorts are a feature of neurodegenerative conditions. A very small number of the countless different proteins found in human biochemistry can become misfolded or otherwise altered in ways that cause them to both (a) precipitate into solid deposits and (b) draw in more of the same proteins to also aggregate. The aggregates further generate a halo of associated biochemistry that is toxic or disruptive to function in brain cells. Aggregates can also spread between cells, as illustrated here. A sizable fraction of the research community in this part of the field is interested in finding ways to interfere in this spreading process, as in principle that could be the basis for a means to prevent these conditions.
Neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's disease, affect different regions of the human brain. Despite these regional differences, research has shown that the processes inside cells affected by these diseases have a lot in common. One characteristic of these diseases is that specific proteins start to form aggregates, or deposits, that damage and eventually kill the cell. In Parkinson's disease, it is misfolded forms of a protein known as α-synuclein that are involved. These aggregates can recruit normal forms of α-synuclein, causing the formation of more protein aggregates.
It has long been known that cells that lie close to each other can create small channels (known as gap junction channels) between them. These small channels are built from members of a family of proteins known as connexins. Studies by other scientists have suggested that connexins play a role in other types of disease,. This led researchers to wonder whether connexins can play a similar role in the spread of Parkinson's disease in the brain.
The brain contains more than 10 connexins, but the study suggests that the protein deposits in Parkinson's disease interact with only one of them, Cx32. Details of the process by which the harmful proteins transfer from one cell to a neighbouring cell with the aid of the channel-forming protein remain unclear. The scientists do know that the channel created by connexin is too narrow for the protein aggregates to pass through. They have shown that the aggregates bind to the channel-forming protein Cx32 and sneak into the cell together with it. When the researchers inhibited the formation of channels in cells in culture, absorption of α-synuclein was prevented. In experiments using brain tissue from four deceased patients diagnosed with Parkinson's disease, the scientists observed a direct binding between synuclein and connexin in two of the cases, which suggests that they interact with each other also in the Parkinsonian brain but not in normal brains.