Summary: Researchers have identified a proteins, TMEM16F, that appears to support the multiply of Parkinson’s disease in the mind. They discovered that a gene in this amino promotes the production of a dangerous form of -synuclein, which travels through nerve cells and creates dangerous Lewy bodies.
Mice without the TMEM16F protein showed reduced disperse of Parkinson’s disease, suggesting this proteins as a possible healing goal. The gene, frequent among Ashkenazi Jews, may provide insights into genetic risk factors and potential treatments. By maybe inhibiting TMEM16F, scientists hope to slow the spread of Parkinson’s.
Important Information:
- TMEM16F gene increases production of harmful α-synuclein, accelerating Parkinson’s unfold.
- Mice lacking TMEM16F showed reduced α-synuclein disease spread.
- Studies suggest TMEM16F as a destination for possible Parkinson’s treatments.
Origin: Tel Aviv University
A novel element in the disease of Parkinson’s condition may be used as a destination for the development of novel therapies for the terrible illness that affects close to 10 million people around the world.
The experts:” We found that a version of the TMEM16F proteins, caused by a genetic gene, enhances the multiply of Parkinson’s disease through nerve cells in the brain”.
Dr. Avraham Ashkenazi and PhD candidate Stav Cohen Adiv Mordechai from the Sagol School of Neuroscience and the University of Medical and Health Sciences at TAU conducted the study. Another participants included: Dr. Orly Goldstein, Prof. Avi Orr-Urtreger, Prof. Tanya Gurevich and Prof. Nir Giladi from TAU’s University of Medical and Health Sciences and the Tel Aviv Sourasky Medical Center, as well as other scientists from TAU and the University of Haifa. The Aufzien Family Center for the Prevention and Treatment of Parkinson’s Disease at TAU supported the study.
The report was published in the medical journal , Aging Cell.
Doctoral scholar Stav Cohen Adiv Mordechai explains:” A essential system of Parkinson’s disease is the formation in brain cells of the protein , α-synuclein , ( in the form of Lewy body ), finally killing these cells.
Researchers have been looking for years to find out how the neurotic form of -synuclein eventually destroys entire brain tissue and spreads through it.
” Since α-synuclein needs to mix the mobile layer in order to spread, we focused on the protein TMEM16F, a controller situated in the body barrier, as a possible drivers of this destructive process”.
At initial, the scientists genetically engineered a rat model without the TMEM16F protein, and derived cells from the hippocampus of these animals for an , in-vitro , mobile unit. Using a specifically engineered disease, they caused these cells to communicate the defective , α-synuclein , associated with Parkinson’s and compared the results with results from normal head cell containing TMEM16F.
The TMEM16F gene was removed, according to the researchers, causing the -synuclein pathology to spread more quickly to less healthy neighboring cells than to normal cells. The results were validated , in-vivo , in a living mouse model of Parkinson’s disease.
In addition, in collaboration with the Neurological Institute at the Tel Aviv Sourasky Medical Center, the researchers looked for mutations (variants ) in the TMEM16F gene that might increase the risk for Parkinson’s disease.
According to Dr. Ashkenazi,” As the incidence of Parkinson’s is known to be relatively high among Ashkenazi Jews, and the Institute conducts a significant ongoing genetic study on Ashkenazi Jews who carry genes that increase the risk of the disease. With their help, we were able to identify a specific TMEM16F mutation which is common in Ashkenazi Jews in general, and in Ashkenazi Parkinson’s patients in particular”.
In contrast to cells carrying the normal gene, pathological -synuclein was found to be secreted more in cells carrying the mutation. The researchers claim that the TMEM16F protein’s biological function contributes to the increase in secretion, which in turn affects membrane secretion processes.
Stav Cohen Adiv Mordechai:” In our study, we discovered a new factor underlying Parkinson’s disease: the protein TMEM16F, which mediates secretion of the pathological α-synuclein protein through the cell membrane to the cell environment.
The defective -synuclein gradually spreads through the brain, causing more and more brain cells to become damaged, and is picked up by healthy neurons nearby. Our findings mark TMEM16F as a possible new target for the development of effective treatments for Parkinson’s disease.
” We may be able to slow down or even stop the spread of the disease through the brain if we can inhibit TMEM16F by inhibiting the secretion of defective -synuclein from brain cells.”
Dr. Ashkenazi emphasizes that research on the new Parkinson’s mechanism has only begun, and quite a number of questions still remain to be explored: Does inhibiting TMEM16F actually reduce the symptoms of Parkinson’s disease? Does the spread of the disease in the brain depend on the cell membranes ‘ lipid content? Is there a link between mutations in TMEM16F and the prevalence of Parkinson’s in the population?
The research team has the intention to continue the investigation in all of these ways.
About this Parkinson’s disease and genetics research news
Author: Noga Shahar
Source: Tel Aviv University
Contact: Noga Shahar – Tel Aviv University
Image: The image is credited to Neuroscience News
Original Research: Open access.
” TMEM16F regulates pathologic α-synuclein secretion and spread in cellular and mouse models of Parkinson’s disease” by Avraham Ashkenazi et al. Aging Cell
Abstract
TMEM16F regulates pathologic α-synuclein secretion and spread in cellular and mouse models of Parkinson’s disease
The spread of the aggregate-prone protein -synuclein ( Syn ) is one of the hallmarks of Parkinson’s disease ( PD ) pathology, which is found in both the patient’s plasma and cerebrospinal fluid as well as the neuronal cell extracellular environment.
The secreted α-syn can exhibit “prion-like” behavior and transmission to naïve cells can promote conformational changes and pathology. The precise role of plasma membrane proteins in the cytoskeletal process of -syn is still a mystery.
The TMEM16 family of lipid scramblases and ion channels has recently been linked to infectious diseases like cancer, but it has not been as well known for its contribution to aging-related illnesses.
We transduced neurons from TMEM16F knockout mice using a reporter system that makes the distinction between donor and recipient neuron of pathologic TMEM16T in order to better understand the role of TMEM16F in TMEM16F in -syn spread.
We found that the spread of α-synA53T was reduced in neurons derived from TMEM16F-knockout mice. These findings were recapitulated in , vivo in a mouse model of PD, where attenuated α-synA53T spread was observed when TMEM16F was ablated.
In addition, we found a single nucleotide polymorphism in Ashkenazi Jewish PD patients ‘ TMEM16F, which gave rise to a missense Ala703Ser mutation with increased lipid scramblase activity.
In cellular PD models, alterations to the regulation of -synA53T extracellular secretion are related to this mutation.
Our study highlights TMEM16F as a novel regulator of α-syn spread and as a potential therapeutic target in synucleinopathies.
