Abnormal proteins found in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s seem to rely on the same mechanism to spread within the brain and disrupt its normal functions, according to a study published in the journal Acta Neuropathologica.
The cellular process described in the study, “Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins,” was found to be shared by all three medical conditions, which suggests it could be an effective target for several neurodegenerative diseases.
Neurodegenerative diseases are caused by the death of brain cells, but they present different symptoms depending on the brain region that is affected. Previous studies have demonstrated that different proteins can be abnormally produced and form clumps in brain cells, with great implications in the development of disease. The proteins involved in this process vary according to each condition: tau in Alzheimer’s, alpha-synuclein in Parkinson’s, and the huntingtin protein in Huntington’s disease.
Recognizing the involvement of these proteins and the underlying mechanism of aggregate protein assembly and spreading are key factors to understanding the progressive nature of the diseases.
Using an experimental in vitro model of alpha-synuclein protein, researchers at Loyola University in Chicago observed that, in the presence of abnormal α-synuclein protein clumps, healthy cells uptake and stored them in small vesicles. This process allows the cells to destroy the abnormal proteins and maintain the healthy and correct environment.
However, the α-synuclein protein clumps could disrupt the enclosure of the vesicles, allowing them to spread within the cell and impairing the cell’s normal functioning.
The “invaded” cell tries to fight this process by promoting signals to destroy both protein clumps and damaged vesicles. But these proteins are very resilient and can resist the degradation signals.
“The cell’s attempt to degrade the proteins is somewhat like a stomach trying to digest a clump of nails,” Edward Campbell, senior author of the study, said in a press release.
Interestingly, the researchers also found that this invasive mechanism was not specific to α-synuclein protein, but was actually common with the tau and the huntingtin proteins. This indicates that preventing this mechanism could impair the progressive development of these neurodegenerative diseases, and others that could share such molecular mechanisms.
“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,” Campbell said.
More studies are still required to further confirm these findings and to address their therapeutic potential for these and other neurodegenerative conditions.
This study was financially supported by grants from the Michael J. Fox Foundation, Parkinson’s Disease Foundation, Illinois chapter of the ARCS Foundation, Arthur J. Schmitt Foundation, and other sources.
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