The Johns Hopkins University School of Medicine researchers identify the role of two proteins Parkin and PINK1 in Parkinson's disease (PD), one of the most common age-related neurodegenerative disorders. The finding may guide the design and development of treatments for PD. The paper, titled "PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival," is published in Cell Reports. PD affects approximately 1% of people aged 60 and above. The incidence has been increasing in recent several decades. The disease progressively impairs a person’s ability to control body movements. Previous studies in mouse models of PD have shown that decreasing the protein PARIS protects against the loss of dopamine-producing neurons. Scientists wonder whether PARIS is associated with other PD-related proteins. According to the new study's lead researcher Prof Ted Dawson, the death of the brain cells that produce dopamine is a hallmark of PD. Dopamine functions as a neurotransmitter in the brain, which helps control the brain's reward and pleasure centers. Dopamine loss leads to the classic symptoms of PD, including muscle tremors, muscle rigidity, decreased mobility, stooped posture, slow voluntary movements, and a mask-like facial expression. It is well established that mutations in the protein Parkin contribute to the death of dopamine neurons. In addition, the protein PINK1 also plays a role in the pathogenesis of PD. Dawson's team set out to study the relationship among the two proteins and PARIS. Previously, Dawson's team discovered that Parkin adds a small regulatory protein called ubiquitin to PARIS, resulting in the breakdown of PARIS. In this work, they identified that PINK1 also interacts with PARIS: PINK1 adds a phosphate group to PARIS, which in turn causes PARIS breakdown. Experiments in human cells and mice showed that decreasing PINK1 led to a significant increase in PARIS. When the researchers increased PINK1 in cultured human cells, they noticed that if PARIS was also increased the cell death was reduced. Collectively, both Parkin and PINK1 induce the breakdown of the PARIS protein and therefore protect brain cells. Mutations in Parkin and PINK1 are known to contribute to PD. Prof Dawson assumed that drugs that target PARIS may be a therapy for PD patients with mutations in Parkin and PINK1. "Altogether, these results uncover a function of PINK1 to direct parkin-PARIS-regulated PGC-1α expression and dopaminergic neuronal survival," the researchers concluded. Researchers from Mayo Clinic also participated in the study. CusAb offers Recombinant Ptpra.
