A study carried out by Loyola University Chicago has revealed that abnormal proteins found in Alzheimer’s disease, Parkinson’s disease and Huntington’s disease all share a similar ability to cause damage when they invade brain cells.The finding could potentially explain the mechanism by which Alzheimer’s, Parkinson’s, Huntington’s and other neurodegenerative diseases spread within the brain and disrupt normal brain functions.

The senior author of the study, Edward Campbell, PhD, first author William Flavin, PhD, and colleagues is published in the journal Acta Neuropathologica.

Campbell explained, “A possible therapy would involve boosting a brain cell’s ability to degrade a clump of proteins and damaged vesicles. If we could do this in one disease, it’s a good bet the therapy would be effective in the other two diseases.”

Neurodegenerative diseases are caused by the death of neurons and other cells in the brain, with different diseases affecting different regions of the brain. Alzheimer’s destroys memory, while Parkinson’s and Huntington’s affect movement. All three diseases are progressive, debilitating and incurable.

Previous research has suggested that in all three diseases, proteins are folded abnormally to form clumps inside brain cells, which spread from cell to cell, eventually leading to cell deaths. Different proteins are implicated in each disease: tau in Alzheimer’s, alpha-synuclein in Parkinson’s and huntingtin in Huntington’s disease.

The researchers focused on how the misfolded protein clumps invade a healthy brain cell. The authors observed that once proteins get inside the cell, they enter vesicles (small compartments that are encased in membranes). The proteins damage or rupture the vesicle membranes, allowing the proteins to then invade the cytoplasm and cause additional dysfunction. (The cytoplasm is the part of the cell that’s outside the nucleus).

The study also demonstrated how a cell responds when protein clumps invade vesicles: The cell gathers the ruptured vesicles and protein clumps together so the vesicles and proteins can be destroyed. However, the proteins are resistant to degradation. “The cell’s attempt to degrade the proteins is somewhat like a stomach trying to digest a clump of nails,” added Campbell.

The results that protein clumps associated with the three diseases cause the same type of vesicle damage was unexpected, claimed Flavin. Loyola researchers initially focused on alpha-synuclein proteins associated with Parkinson’s disease. As a result, they asked collaborator Ronald Melki, PhD, to send them samples of different types of alpha-synuclein. To do the experiment in a blinded, unbiased manner, the researchers did not know which types of alpha-synuclein were which. Without telling the researchers, Melki, a protein researcher at the Paris-Saclay Institute of NeuroScience, sent other types of proteins as well. This led to the surprise finding that tau and huntintin proteins can also damage vesicles.

To conclude, Campbell emphasised that the findings need to be followed up and confirmed in future studies.