Decades of research on Parkinson’s disease have implicated neuronal protein aggregates in the spread of the disorder. Now, researchers have identified lysosomal exocytosis as being responsible for the release of these aggregates and their pathogenic reproduction in the brain.
If there are treatments to attenuate certain anomalies of the movementmovement characteristics of the Parkinson’s disease, none of them can to date stop the progression of this neurological disorder. The reason is the lack of knowledge about this process.
Update of previous results
The last decades of research on the Parkinson’s diseaseParkinson’s disease have shown that the death of neurons in affected people was associated with the release of pathogenic neuronal protein alpha-synuclein (αSyn) aggregates into the extracellular space. The researchers hypothesized that this release of aggregates triggered the chain of disease spread from one neuron to another.
Previous experiments in mice and primatesprimates Non-humans have shown that injection of these aggregates into the brainbrain could trigger this spread, as well as neurodegeneration similar to that of Parkinson’s disease. However, the way neurons transmit these aggregates to other neurons has never been detailed before.
Explanation of the process of lysosomal exocytosis
researchers from Medicine Weill Cornell used mouse models of Parkinson’s disease in which aggregates of αSyn occur within neurons. Their results, published in NatureCommunicationsshow that these aggregates accumulate in cellular vesicles: lysosomeslysosomes. These normally contain enzymesenzymes able to digest and RecycleRecycle since moleculesmolecules What wastewaste cell phone.
But the process doesn’t work well with aggregates of αSyn, which are often bound together in a tightly layered structure called “amyloid.” By a process of lysosomal exocytosis, the lysosome moves to the cellular membranecellular membrane and merges with it, and its contents are then flushed out of the cell.
In fact, neurons release αSyn aggregates, which lack a membrane and are able to reproduce. ” These results propose lysosomal exocytosis as a central mechanism for the release of proteins that aggregate and are resistant to degradation by neurons. summarize the authors.
A therapeutic approach against neurodegenerative diseases
To get closer to a cure for Parkinson’s disease, the researchers showed in other experiments that by reducing the rate of lysosomal exocytosis, they could reduce the concentration of propagative aggregates. Keeping these aggregates within lysosomes could be an interesting strategy.
Already known, the process of lysosomal exocytosis would be a general mechanism for the propagation of protein aggregates in neurodegenerative diseases such as Parkinson’s disease. It would therefore be a general target of choice for the development of treatments and preventive measures. In this sense, the research team is currently investigating the role of lysosomes in the Alzheimer disease.