Researchers found that clumps of faulty protein involved in Alzheimer’s, Parkinson’s, and Huntington’s disease cause brain damage by invading and rupturing small vesicles in neurons.
The study, “Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins,” published in the journal Acta Neuropathologica, bring to light insights that can be used in the development of new therapies against protein aggregation and neuronal damage in neurodegenerative disorders.
Aggregation refers to faulty proteins that form clumps within neurons. Alzheimer’s disease is characterized by aggregates of the tau protein, Parkinson’s disease is marked by the production of alpha-synuclein clumps, and Huntington’s disease is caused by aggregates of the huntingtin protein.
“A possible therapy would involve boosting a brain cell’s ability to degrade a clump of proteins and damaged vesicles,” Edward Campbell, PhD, and the study’s senior author, said in a news release. “If we could do this in one disease, it’s a good bet the therapy would be effective in the other two diseases.”
Researchers wanted to know how protein aggregates spread from cell to cell, impairing neuronal activity and triggering neuronal death. Using an imaging-based assay, they found that once alpha-synuclein aggregates reach a healthy neuron, they invade and rupture the neuron’s vesicles (small compartments that are used for the transport of molecules inside cells), disturbing the neuron’s normal activity.
The affected neuron responds by gathering the damaged vesicles and protein aggregates together so that they can be degraded. But the aggregates are resistant to degradation.
“The cell’s attempt to degrade the proteins is somewhat like a stomach trying to digest a clump of nails,” Campbell said.
According to researchers, the ability to induce vesicle rupture was not specific to alpha-synuclein. In fact, protein aggregates behave in a similar way among the three diseases, be it tau, alpha-synuclein, or huntingtin.
The team identified markers of vesicle rupture caused by alpha-synuclein in brain sections from Parkinson’s disease patients, but also found that tau and huntingtin can damage vesicles as well.
Together, these findings support the idea that vesicle rupture is a damaging mechanism triggered by aggregates of multiple neurodegenerative disease-associated proteins.
According to Campbell, results of this study need to be followed up and require confirmation from future studies.
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