In the treatment of the Parkinson’s disease, a new drug combo could fix the enzymatic path lysosomal disrupted in brain cells affected by theLto pathology, according to a study by a group of Northwestern Medicine experts.
Improving the transport of these enzymes can increase the function lysosominal, helping theorganelle mobile phone to break down the harmful protein aggregates that are a primary cause of symptoms in Parkinson’s disease (PD), according to Joseph Mazzulli, Ph.D., associate professor at the Ken and Ruth Davee Department of Neurology in the Division of Movement Disorders.
The results of the Research have been published in the scientific journal Neuron.
New drug combo to treat Parkinson’s disease: here’s how it works
Joseph Mazzulli, based on the study of the new combo of uril drugs to treat Parkinson’s, said: ” We think that going forward, these combination therapies will be very effective. “
A defining feature of Parkinson’s disease is the accumulation of proteinsalpha-synucleins misfolded in the brain. These proteins aggregate and form lumps which are linked to a variety of damaging effects including oxidative stress, inflammation and mitochondrial dysfunction.
A previous study also developed by the Mazzulli laboratory found that the lysosome, an organelle responsible for the disposal of waste in the cell, was hampered byalpha-synuclein. In this study, the scientists previously looked at this path by observing the impact of alpha-synuclein on the endoplasmic reticulum (ER).
The ER is where proteins are initially synthesized and folded, including important enzymes required for proper lysosome function. Here, alpha-synuclein binds to the ER and inhibits folding, leading to the accumulation of malformed proteins that are unable to exit the ER to their next organelle destination.
Using patient-derived midbrain neurons that model disease, Mazzulli and his collaborators found that an FDA-approved drug, the diltiazem, can restore proper folding and prevent enzyme aggregation.
“It actually improves the activity of what we call ‘folding companions“And dissolves the aggregates into functional components, so that they can leave the emergency room”, Mazzulli specified.
These enzymes travel to the Golgi apparatus, which packs and ships materials throughout the cell. Here, too, alpha-synuclein interferes with function, reducing the amount of proteins or enzymes that can pass through the Golgi. However, it has been shown that another drug, a inhibitor of farnesyl-transferase, restores the correct Golgi activity.
“This complex actually opens multiple lanes on the highway through the Golgi“Said Mazzulli.
Combo application of the drugs to patient-derived Parkinson’s neurons restored lysosome function and allowed to the organelle to dispose of the alpha-synuclein, a finding that could potentially reduce symptoms in patients.
Importantly, these results show that the Therapeutic strategies targeting multiple branches of this protein synthesis and disposal route will have a better chance of successfully treating the diseaseMazzulli said.
“We must attack in this approach on several fronts “, concluded the scientist.
Parkinson’s disease is the second most common age-related neurodegenerative disease after Alzheimer’s disease. It is estimated that seven to ten million people worldwide suffer from Parkinson’s disease. The prevalence of the disease ranges from 41 in 100,000 people in the fourth decade of life to more than 1,900 in 100,000 people over 80.
The incidence of the disease, or the rate of newly diagnosed cases, generally increases with age, although it may stabilize in people over the age of 80. It is estimated that 4% of people with Parkinson’s are diagnosed before the age of 50.
Men are 1.5 times more likely to have Parkinson’s than women. The disease affects patients’ quality of life, making social interaction more difficult and worsening their economic conditions due to the medical costs associated with the disease.
Population studies of Parkinson’s incidence are important for scientists to understand the history of the disease, its progression and associated risk factors. Information on incidence in different age and gender groups can help scientists around the world design strategies to meet the needs of individuals diagnosed with PD.
#Parkinsons #combination #drugs #reduces #toxic #aggregates