An error leading to the death of neurons in Parkinson's disease has been found

Researchers at Albert Einstein College of Medicine, part of Yeshiva University, have identified the most common mutation found in patients with familial Parkinson's disease. This discovery raises hopes for the emergence of effective treatments for both familial and more common sporadic forms of this disease.

Parkinson's disease is a gradually progressive neurodegenerative disease that leads to impaired motor functions. The most common mutations causing the familial form of Parkinson's disease are localized in the gene of the enzyme "leucine repeat-enriched kinase 2" (LRRK2). These mutations lead to the synthesis of abnormal variants of the LRRK2 protein, but how this is related to the occurrence of microscopic symptoms of the disease – the formation of abnormal protein aggregates in dopamine–producing neurons of the brain - has not yet been clear.

According to the head of the study, Professor Ana Maria Cuervo, it turned out that the appearance of abnormal forms of LRRK2 leads to disruption of an important process that ensures the disposal of protein waste in cells, including alpha-synuclein protein, which is the main component of protein aggregates accumulating in the affected neurons of patients with Parkinson's disease.

The process suffering from this disease is known as autophagy, mediated by chaperone proteins. This mechanism of autophagy involves special molecules that "transmit" old and damaged protein molecules into lysosomes – membrane structures filled with enzymes that break down protein molecules into amino acids, which are subsequently used for the synthesis of new proteins.

The authors conducted a series of experiments on cultures of neurons isolated from the brain tissue of four mouse models and patients with Parkinson's disease with LRRK2 gene mutations, as well as neurons obtained using induced pluripotent stem cell technology from skin cells of patients with this disease. The results obtained showed that in the presence of abnormal forms of the LRRK2 protein, this type of autophagy is inhibited. The result is insufficient cleavage of alpha-synuclein, which accumulates inside nerve cells to toxic levels.

Currently, researchers are looking for possible methods to increase the activity of this protein utilization system, which would help prevent or delay damage and death of neurons. They have already started testing several chemical compounds and the preliminary results obtained look very encouraging.

Article by Samantha J Orenstein et al. Interplay of LRRK2 with chaperone-mediated autophagy is published in the journal Nature Neuroscience.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Albert Einstein College of Medicine:
Scientists Identify 'Clean-Up' Snafu that Kills Brain Cells in Parkinson's Disease.

06.03.2013