Parkinson’s reflection? One drug that brings back the brain cells that die to life

The genetic mutation causes an enzyme called Kinaz 2, LRRK2 or LRRK2. Many of the activity of the LRRK2 enzyme changes the structure of the brain cells in a manner that disrupts decisive communication between the neurons that make the dopamine and cells in the scheme, which is a deep region in the brain that forms part of the dopamine system and involved in movement, motivation and decision -making.

“The results of this study indicate that the inhibition of Lrk2 enzyme can settle on the development of symptoms if patients can be identified early enough,” said Susan Bakhbver, Professor Emma Vitver Merner in Medical Sciences and Professor of Biochemistry. Excessive LRRK2 researchers can be active using the MLI-2 LRRK2 inhibitor, a molecule attached to the enzyme and reduces its activity.

PFEFFer added that since the genetic mutation is not the only way to end the excessive active LRRK2 enzyme, the treatment of the barrier in other types of Parkinson’s disease or even other neurological degenerative diseases may help.

PFEFFer is the first author of the study published in Science signs On July 1. Ebsy Jaimon, PhD, post -PhD researcher in biochemistry, is the main author. This work is part of a long cooperation with Dario Alesi, PhD, at Dundy University in Scotland.

Cellular antennas

About 25 % of Parkinson’s disease caused by genetic mutations, and the only genetic mill that makes the Lrk2 enzyme very active is one of the most common. Excessive LRRK2 enzyme leads to the loss of cells their initial cilia, a cellular attachment like antenna, sending and receiving chemical messages. The cell that lost its basic cilias is similar to your mobile phone when the network decreases – there are no messages or are sent.

In a healthy brain, many messages are sent back and forth between dopamine neurons in an area of ​​the brain called black and planned. These cellular “conversations” are possible because the axes of dopamine neurons, which are tuberculosis extensions from the cell body, reach the extended to communicate with neurons and crimes, and cells that support the function of neurons.

An important connection that is disrupted by the LRRK2 enzyme activity occurs a lot when dopamine neurons are emphasized and a signal release in the chart called the vocal hedgehog (named after the animated character). In the healthy brain, some neurons and star cells cause a type of glial support cell, in the plan to produce proteins called neurological protection factors. As their name suggests, these proteins help protect other cells from death. When there is a lot of LRRK2 enzyme activity, many professional cells lose their initial cilia – and their ability to receive a reference from dopamine neurons. This disorder in audio hedgehogs means that neurological prevention factors are not produced.

“Many types of processes needed for cells are organized to stay through the cilia of transmission and reception. Cells in the scheme that secretes neurological factors in response to the cage signals also need the hedgehog to survive.

The recovered cities were unexpected

The aim of the study was to test if the MLI-2 LRRK2 inhibitor was a lot of the effects of the LRRK2 enzyme activity. Since the neurons and crimes examined in this study were completely mature and no longer multiply through the division of cells, the researchers at first were not sure whether the cilia could grow. By working with mice with the genetic mutation that causes excessive LRRK2 activity and symptoms that are consistent with Parkinson’s early disease, scientists first tried to feed the barrier mice for two weeks. There were no changes in the structure of the brain, signal, or dopamine neurons.

Recent results on neurons participating in organizing daily rhythms, or sleeping courses that obey sleep, inspired the researchers to try again. The initial cilia on those cells – which are no longer divided – has grown and shrinking every 12 hours.

Feer said: “The results that other non -advanced cells that grow cilia caused us to realize that it was theoretically possible that the inhibitor would work.”

The team decided to see what happened after the excessive activity of the enzyme Lrk2 mice consumed the prevention of a longer period of time; PFEFFer described the results as “amazing”.

Three months after eating the barrier, the percentage of absolute nerve cells and crimes that are usually affected by the excessive activity Lrk2 enzyme that had raw cilia in mice with a genetic mutation that could not be distinguished from those in mice without a genetic mutation. In the same way that the transition from an area with intermittent cell service is transmitted to one with a good service, it restores our ability to send and receive text messages, and to increase the basic communication restored between dopamine and scheme neurons.

Disclated nerve cells and crimes once again secreted neurological prevention factors in response to the hedgehog sign of dopamine neurons in the same amounts of mice brains without a genetic mutation. The hedgehog signals decreased from dopamine neurons, indicating that they were under less pressure. The indicators of the density of the neuroplastic neurotransmitters have multiplied inside the scheme, indicating a preliminary recovery of the nerve cells that were in the stage of death.

“These results indicate that it may be possible to improve the condition of patients with Parkinson’s disease.”

The first symptoms of Parkinson’s disease begin about 15 years before someone notices the tremor. These symptoms are usually the loss of smell, constipation and sleep disturbance in which people behave their dreams while still sleeping, according to PFEFFer. Hope is that people with a genetic mutation Lrk2 can start a treatment that prevents enzyme as soon as possible.

The next step for the search team is to test if other forms of Parkinson’s disease are not associated with the Lrk2 genetic mutation can benefit from this type of treatment.

“We are very enthusiastic about these results. They suggest that this approach has a great promise to help patients in terms of restoring nervous activity in this brain circle.” “There are many clinical trials of LRRK2 inhibitors, and we hope that these results in mice are applied to future patients.”

The study was funded by the Michael J Fox Research Foundation, the alignment sciences through the Parkinson’s Initiative and the UK Medical Research Council.