Moderating Impulsivity: Train the Brain to Stop the Train

 NOVEMBER 16, 2018 Dr. CBY DR. C

Brain training happens all the time. The goal of Parkinson’s disease (PD) rehabilitation is to use training to limit the effects of the condition. When training the brain, it is important to be mindful of what it is doing while implementing a practice of mental attentiveness. This specific type of mindfulness is aimed at compensating for issues connected to PD. The rehab program seeks to put a skilled conductor inside our brain, one who is trained to slow down, and eventually stop, the impulsivity train.

The application of mindfulness as mindfulness-based stress reduction (MBSR) has yet to provide clear scientific evidence for its efficacy in treating Parkinson’s patients. The problem is that these studies are poorly designed. However, this is not the same as saying mindfulness is unhelpful. Mindfulness, when practiced frequently, may result in changing the brain structure in PD patients.

To train the brain to stop the train of impulsivity, we act and think in a new way to change the structure of the brain. It is made to be plastic and to change in response to what we do with it.

When properly applied to PD and impulsivity, mindfulness is composed of three parts: mental attentiveness (focusing attention where it is needed), slowing down the impulse, and changing the course. When putting a rehabilitation plan in place, mindfulness, using these three components, should be directed at the triggers of impulsivity and its three checkpoints (see the diagram below, which was explained in my previous column).

The following table below explains the application of mindfulness to impulsivity:

Graphic by Dr. C (T.O.O.T.S. refers to Time Out On The Spot)

The key to impulsivity management is to eventually turn the training into a habit — to almost automate responses to the heightened responses that occur at each checkpoint. This is how we put our brain train conductor to work to stop the train of impulsivity (or at least slow it down) most of the time.

What have you found to be successful in controlling your impulsivity?

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Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

https://parkinsonsnewstoday.com/2018/11/16/parkinsons-disease-train-brain-stop-moderating-impulsivity-mindfulness-brain-structure/

For First Time, Precursors of Dopamine Neurons Implanted in Brain of Parkinson’s Patient

NOVEMBER 16, 2018 BY JOSE MARQUES LOPES, PHD 

Precursors of dopamine-producing cells were implanted into the brain of a Parkinson’spatient for the first time. The patient in Japan is the first of seven to receive this experimental therapy.

The approach uses induced pluripotent stem cells (iPSCs), which are developed by reprogramming cells collected from the skin or blood of adults so that they revert to a stem cell-like state and are able to differentiate into almost any cell type.

Scientists at Kyoto University can transform iPSCs into precursors of dopamine-producing neurons. In Parkinson’s, progressive loss of these neurons in a brain area called substantia nigra, and reduced dopamine release in a connected region called striatum, lead to the characteristic motor symptoms.

Last month, neurosurgeon Takayuki Kikuchi implanted 2.4 million dopamine precursor cells into the brain of a Parkinson’s patient in his 50s. The team implanted the cells into 12 centers of dopamine activity over three hours. Stem cell researcher Jun Takahashi and colleagues derived the dopamine precursor cells from iPSCs originally developed from skin cells of an anonymous donor.

“The patient is doing well and there have been no major adverse reactions so far,” Takahashi said in a Nature press release, written by David Cyranoski. The man will be observed over six months. If he does not develop complications, an additional 2.4 million dopamine precursor cells will be implanted into his brain.

Six more Parkinson’s patients are expected to receive this stem cell therapy, which will allow researchers to collect safety and efficacy data by the end of 2020. According to Takahashi, the treatment could reach the market as early as 2023 under Japan’s fast-track approval system for regenerative medicines. “Of course it depends on how good the results are,” he said.

In 2017, Takahashi and his team showed that dopamine-producing neurons transplanted into the brains of monkeys enabled them to move spontaneously over two years. Also, the transplanted cells did not lead to abnormal and jerky movements (dyskinesia), did not develop into tumors — a key concern with iPSCs-based treatments — and did not trigger an immune response not treatable with an immunosuppressive therapy.

In 2014, a Japanese woman in her 70s became the first patient to receive retinal cells derived from iPSCs to treat an eye condition called age-related macular degeneration.

https://parkinsonsnewstoday.com/2018/11/16/precursors-dopamine-neurons-implanted-parkinsons-patients-brain/

UNS’ Investigational Vaccine UB-312 Holds Potential to Prevent Parkinson’s, Other Neurological Diseases, Data Show

NOVEMBER 16, 2018 BY ALICE MELÃO 

An investigational vaccine being developed by United Neuroscience (UNS) presented several advantages over traditional vaccines to treat progressive disorders, such as Parkinson’s disease, according to preclinical data.

The vaccine, called UB-312, was more selective to prevent toxic aggregates of alpha-synuclein in mouse models of the disease.

These latest findings were discussed during the Parkinson’s UK Research Conference 2018 held in York, England. The presentation “Anti-alpha synuclein active immunotherapy in Parkinson’s disease,” was given by Hui Jing Yu, PhD, medical director of UNS.

“We are very pleased with the promising results of UB-312 in both in vitro and in vivo preclinical studies, which supports our efforts to develop a convenient and cost-effective treatment for Parkinson’s disease,” Jing Yu said in a press release.

“With this platform, and thanks to the wonderful opportunity to participate in the Parkinson’s UK Research Conference, we will continue driving forward our efforts to improve the lives of millions of people suffering from neurodegenerative disorders,” she added.

To date, no safe and effective vaccine targeting disease-related forms of alpha-synuclein has been developed.

UNS is using its proprietary technology platform, UBITh, to develop a new generation of vaccines that enable more people, including elderly patients with weakened immune systems, to respond more robustly, more specifically, and with fewer side effects.

Its vaccines are designed to train a patient’s own immune cells to produce specific antibodies, also known as endobodies, that will target natural proteins that have started to behave abnormally and resulting in chronic diseases.

Preclinical studies have shown that UB-312-induced antibodies preferentially bind to disease-related forms of alpha-synuclein, prevent their aggregation, and even promote their disaggregation. This inhibition occurred while preserving motor function, body weight, and survival in mouse models of alpha-synuclein-mediated disease.

The potential therapeutic activity of UB-312 also was successfully assessed in brain tissue samples collected post-mortem from patients with Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy.

“Aggregated alpha-synuclein plays a prominent role in multiple disorders of cognition, movement and autonomic function. The ability of UB-312 antisera to target toxic alpha-synuclein species in several disorders will allow us to address multiple neurodegenerative conditions including Parkinson’s disease,” said Ajay Verma, MD, PhD, chief medical officer of UNS.

The company already has initiated an observational study to establish a biomarker to determine UB-312’s potential in a trial-ready group of Parkinson’s patients in the United Kingdom. It also is planning to launch a Phase 1 trial in The Netherlands to explore the clinical activity of UB-312 by 2019.

“Expansion of UNS’ proprietary ‘Endobody’ vaccine technology platform to other targets affirms our goal of becoming a global leader in neurodegenerative disorders and asserts our vision of democratizing brain health,” said Mei Mei Hu, UNS’ CEO.

UNS’ lead vaccine candidate UB-311, which was developed to target amyloid-beta protein aggregates, is currently in clinical development in an ongoing Phase 2 trial (NCT02551809) in patients with mild Alzheimer’s disease.

https://parkinsonsnewstoday.com/2018/11/16/vaccine-ub-312-may-prevent-parkinsons-other-diseases-data-show/

Personalized Tissue Implants From Patients’ Own Cells Have Potential to Treat Parkinson’s, Study Suggests

 NOVEMBER 15, 2018 BY JOSE MARQUES LOPES, PHD

A new, fully personalized tissue implant using a patient’s own materials and cells can regenerate any organ in the body with minimal risk of an immune response, according to researchers who are now exploring the approach as a potential way to treat Parkinson’s disease.

The new technique was reported in the study, “Personalized Hydrogels for Engineering Diverse Fully Autologous Tissue Implants,” published in the journal Advanced Materials.

Engineered tissue implants normally use scaffolding materials such as hydrogels, which provide physical support to cells while also supplying the necessary environment for cellular assembly and function. The materials may be synthetic or natural.

After transplant, these materials may induce an immune response in the host that can lead to rejection of the implanted tissue. As a result, immunosuppressant medications, which inhibit the activation of the immune system, may be necessary throughout the patient’s life even when using DNA-free materials.

Induced pluripotent stem cells (iPSCs), generated from the patient’s own cells, may be used to screen treatment candidates and as personalized cell therapies. These iPSCs are derived from either skin or blood cells that have been reprogrammed back into a stem cell-like state, allowing for the development of an unlimited source of any type of human cell needed for therapeutic purposes.

A gelatinous protein mixture called Matrigel is currently the most used supporting microenvironment for iPSCs. However, because it is derived from the sarcoma tumors of mice, its safety in humans is unknown.

In this study, a team from Tel Aviv University (TAU) collected a small biopsy of a highly vascularized fatty tissue called omentum from healthy human donors or from pigs. This tissue serves as a depot for stem cells.

They separated the cells from the extracellular matrix (ECM) — which provides structural and biochemical support to cells — so that the ECM could be integrated into a temperature-responsive, personalized 3D hydrogel, and the cells could be engineered to become pluripotent, meaning they can give rise to almost all cell types in the body.

Undifferentiated cells were then enclosed within the hydrogel, later generating cardiac muscle cells called cardiomyocytes, neurons of the cerebral cortex, motor neurons (which regulate muscle contraction), endothelial cells (which line the interior of blood vessels), or adipocytes.

After combining the resulting stem cells and the hydrogel, scientists successfully engineered tissue samples and tested potential immune responses first in a laboratory dish and then in vivo, by transferring implants from pigs or mice into a specific mouse strain. Results showed less inflammation when transplants were made within mice.

“With our technology, we can engineer any tissue type, and after transplantation we can efficiently regenerate any diseased or injured organ — a heart after a heart attack, a brain after trauma or with Parkinson’s disease, a spinal cord after injury,” Tal Dvir, PhD, the study’s senior author and a professor at TAU’s Department of Biotechnology, Department of Materials Science and Engineering, said in a press release. “In addition, we can engineer adipogenic (fatty tissue) implants for reconstructive surgeries or cosmetics.”

“This versatile bioengineering approach may assist to regenerate any tissue and organ with a minimal risk for immune rejection,” the researchers wrote in the study.

They are now attempting to regenerate an injured spinal cord and an infarcted heart with spinal cord and cardiac implants, respectively. They are also studying the potential of human dopamine-producing cell implants to treat Parkinson’s in animal models. The gut and the eyes are among other targets for regeneration.

https://parkinsonsnewstoday.com/2018/11/15/personalized-tissue-implants-using-patients-cells-potential-parkinsons-treatment/

Astilbin, Found in Plants, Protects Neurons and Improves Motor Control, Mouse Study Finds

NOVEMBER 15, 2018 BY JOANA CARVALHO 

A compound found in various types of plants, called astilbin, can protect neurons by preventing over-activation of glia cells (nerve cells that support neurons), excessive alpha-synuclein production, and oxidative stress, researchers working in a mouse model of Parkinson’s disease report.

Their study, “Neuroprotective effects of Astilbin on MPTP-induced Parkinson’s disease mice: Glial reaction, α-synuclein expression and oxidative stress,” was published in International Immunopharmacology.

Parkinson’s disease is mainly caused by the gradual loss of dopaminergic neurons in the substantia nigra, a region of the brain responsible for movement control.

The disease also seems to be associated with over-production of the protein alpha-synuclein in nerve cells of the brain. When this protein clumps together, it gives rise to small toxic deposits inside brain cells, inflicting damage and eventually killing them.

Parkinson’s characteristic symptoms are related to the resulting loss of dopamine-producing nerve cells, and its therapies typically focus on restoring dopamine signaling in the brain to ease problems with movement and balance.

Astilbin, a flavanonol also found in alcoholic beverages (it’s a constituent of wine grape), is known to possess anti-inflammatory, anti-oxidant, and neuroprotective properties.

For this reason, a team of Chinese researchers tested whether astilbin could protect neurons from damage in mice chemically induced to develop Parkinson’s disease.

Researchers injected animals with MPTP — a neurotoxin that has been shown to trigger Parkinson’s symptoms in mice and non-human primates — once a day for five days. Once the animals showed classic Parkinson’s symptoms of motor impairment, they were treated with either astilbin or a saline solution (as a control group) for another seven days.

Behavioral tests revealed that mice given astilbin showed a remarkable improvement in motor function compared to control animals, with significant differences seen in movement scores on a pole and traction test between treated and untreated diseased mice.

Biochemical and molecular analysis also showed that astilbin blocked the drop in dopamine brain levels that’s associated with MPTP treatment, minimized the loss of dopaminergic neurons and the activation of glia cells in the substantia nigra, prevented over-production of alpha-synuclein, and reduced oxidative stress — the cellular damage that occurs as a consequence of high levels of oxidant molecules.

Moreover, researchers reported that astilbin activated PI3K/Akt signaling — a chemical cascade involved in the survival and growth of dopaminergic neurons — in the brain after MPTP administration. This finding suggests, they wrote, “that treatment with AST [astilbin] prevents the loss of dopaminergic neurons in MPTP-induced PD [Parkinson’s disease] mice by inducing the activation of the PI3K/Akt signaling pathway.”

Astilbin “exerts neuroprotective effects” on the diseased mice “by suppressing gliosis [activation of glia cells], α-synuclein overexpression and oxidative stress, suggesting that AST could serve as a therapeutic drug to ameliorate PD,” the researchers concluded.

https://parkinsonsnewstoday.com/2018/11/15/compound-in-plants-called-astilbin-protects-neurons-improves-motor-control-in-parkinsons-mouse-model/

VPS35 Gene and Parkinson's Disease

NOVEMBER 15, 2018          By Angela Betsaida B. Laguipo, BSN

Parkinson’s disease (PD) is a progressive condition that affects the nervous system, particularly the part of the brain responsible for movement. Whilst PD has no known cause, it has previously been linked to mutations in the VPS35 gene.

Parkinson’s disease is a neurodegenerative condition that affects the dopamine-producing brain cells in the brain area dubbed as the substantia nigra. The disease leads to various movement problems, including tremor, limb or muscular rigidity, bradykinesia, imprecise movements, and gait or balance problems.

An estimated 10 million people are living with Parkinson’s disease across the globe. In the United States, about one million people have the disease, with 60,000 Americans being diagnosed each year. However, some patients go undiagnosed until advanced stages of disease are present.

Men have a 50% higher risk of developing the disease compared with women. In most cases, symptoms begin after the age of 50 years. However, 4% to 5% of patients experience symptoms before the age of 40. When the symptoms appear between the ages of 21 and 40, it is referred to as Young-onset Parkinson’s disease.

Parkinson’s disease etiology

To understand Parkinson’s disease, it is important to understand how neurons work. The brain controls all processes in the human body. Nerve cells (neurons) send and receive nerve impulses between the brain and all parts of the body. These impulses, or messages, help the body communicate with the brain as its control center.

The neurons contain dendrites, which are branching arms. They serve as antennae to pick up signals and messages. Once a message is received, the neuron’s axon carries the messages away from the body of the cell. In this way, nerve impulses travel through neurons, from the axon of one nerve cell to the dendrites of the next.

The travel of the messages from one neuron to another is made possible, thanks to a tiny gap between them called a synapse. For a message to cross the gap, neurotransmitters (chemical messengers) are needed.

In people with Parkinson’s disease, there is an abnormally low level of dopamine, which is one of these chemical messengers that sends signals around the body to control movement. The low dopamine levels in Parkinson’s disease result from death of dopaminergic neurons, a type of nerve cells, in the substantia nigra.

When there are low levels of dopamine, people find it difficult to control their movements, including simple activities like walking.

How is VPS35 involved in Parkinson’s disease?

Aside from environmental and genetic factors associated with the development of Parkinson’s, gene mutations have appear to play an important role in the progression of this neurodegenerative disease.

Recently, a new gene has been associated with PD. Identification of the VPS35, or vacuolar protein sorting 35 homolog, gene has provided new insights into the disease process involved in PD. Various studies have shown that the VPS35 gene is associated with late-onset, autosomal dominant familial Parkinson’s disease.

Autosomal dominant inheritance is also seen with alpha-synuclein-SNCA and LRRK2 genes, which have also been associated with PD. Autosomal recessive inheritance of Parkin, DJ1, or PINK1 genes has also been associated with PD.

Although the exact mechanism by which PD develops remains unclear, understanding more about the gene can lead to the development of proper therapeutic strategies.

https://youtu.be/YBzakbb3jls

Sources:

• https://www.parkinsonassociation.org/facts-about-parkinsons-disease/
• https://www.nia.nih.gov/health/parkinsons-disease
• www.ninds.nih.gov/.../Parkinsons-Disease-Information-Page
• https://www.ncbi.nlm.nih.gov/pubmed/28222538
• https://www.sciencedirect.com/science/article/pii/S0896627314010812
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438477/

https://www.news-medical.net/health/VPS35-Gene-and-Parkinsons-Disease.aspx

Playing high school football changes the teenage brain

 November 16, 2018 by Kara Manke, University of California - Berkeley

Magnetic resonance imaging (MRI) brain scans have revealed that playing a single season of high school football can cause microscopic changes in the grey matter in young players' brains. These changes are located in the front and rear of the brain, where impacts are most likely to occur, as well as deep inside the brain. Credit: Nan-Jie Gong and Chunlei Liu, UC Berkeley

A single season of high school football may be enough to cause microscopic changes in the structure of the brain, according to a new study by researchers at the University of California, Berkeley, Duke University and the University of North Carolina at Chapel Hill.

The researchers used a new type of magnetic resonance imaging (MRI) to take brain scans of 16 high school players, ages 15 to 17, before and after a season of football. They found significant changes in the structure of the grey matter in the front and rear of the brain, where impacts are most likely to occur, as well as changes to structures deep inside the brain. All participants wore helmets, and none received head impacts severe enough to constitute a concussion.

The study, which is the cover story of the November issue of Neurobiology of Disease, is one of the first to look at how impact sports affect the brains of children at this critical age. This study was made available online in July 2018 ahead of final publication in print this month.

"It is becoming pretty clear that repetitive impacts to the head, even over a short period of time, can cause changes in the brain," said study senior author Chunlei Liu, a professor of electrical engineering and computer sciences and a member of the Helen Wills Neuroscience Institute at UC Berkeley. "This is the period when the brain is still developing, when it is not mature yet, so there are many critical biological processes going on, and it is unknown how these changes that we observe can affect how the brain matures and develops."

Concerning trends

One bonk to the head may be nothing to sweat over. But mounting evidence shows that repeated blows to the cranium—such as those racked up while playing sports like hockey or football, or through blast injuries in military combat—may lead to long-term cognitive decline and increased risk of neurological disorders, even when the blows do not cause concussion.

Over the past decade, researchers have found that an alarming number of retired soldiers and college and professional football players show signs of a newly identified neurodegenerative disease called chronic traumatic encephalopathy (CTE), which is characterized by a buildup of pathogenic tau protein in the brain. Though still not well understood, CTE is believed to cause mood disorders, cognitive decline and eventually motor impairment as a patient ages. Definitive diagnosis of CTE can only be made by examining the brain for tau protein during an autopsy.

These findings have raised concern over whether repeated hits to the head can cause brain damage in youth or high school players, and whether it is possible to detect these changes at an early age.

"There is a lot of emerging evidence that just playing impact sports actually changes the brain, and you can see these changes at the molecular level in the accumulations of different pathogenic proteins associated with neurodegenerative diseases like Parkinson's and dementia," Liu said. "We wanted to know when this actually happens—how early does this occur?"

A matter of grey and white

The brain is built of white matter, long neural wires that pass messages back and forth between different brain regions, and grey matter, tight nets of neurons that give the brain its characteristic wrinkles. Recent MRI studies have shown that playing a season or two of high school football can weaken white matter, which is mostly found nestled in the interior of the brain. Liu and his team wanted to know if repetitive blows to the head could also affect the brain's gray matter.

"Grey matter in the cortex area is located on the outside of the brain, so we would expect this area to be more directly connected to the impact itself," Liu said.

The researchers used a new type of MRI called diffusion kurtosis imaging to examine the intricate neural tangles that make up gray matter. They found that the organization of the gray matter in players' brains changed after a season of football, and these changes correlated with the number and position of head impacts measured by accelerometers mounted inside players' helmets.

The changes were concentrated in the front and rear of the cerebral cortex, which is responsible for higher-order functions like memory, attention and cognition, and in the centrally located thalamus and putamen, which relay sensory information and coordinate movement.

"Although our study did not look into the consequences of the observed changes, there is emerging evidence suggesting that such changes would be harmful over the long term," Liu said.

Tests revealed that students' cognitive function did not change over the course of the season, and it is yet unclear whether these changes in the brain are permanent, the researchers say.

"The brain microstructure of younger players is still rapidly developing, and that may counteract the alterations caused by repetitive head impacts," said first author Nan-Ji Gong, a postdoctoral researcher in the Department of Electrical Engineering and Computer Sciences at UC Berkeley.

However, the researchers still urge caution—and frequent cognitive and brain monitoring—for youth and high schoolers engaged in impact sports.

"I think it would be reasonable to debate at what age it would be most critical for the brain to endure these sorts of consequences, especially given the popularity of youth football and other sports that cause impactto the brain," Liu said.

More information:Nan-Jie Gong et al, Microstructural alterations of cortical and deep gray matter over a season of high school football revealed by diffusion kurtosis imaging, Neurobiology of Disease(2018). DOI: 10.1016/j.nbd.2018.07.020

Journal reference: Neurobiology of Disease 

Provided by: University of California - Berkeley

https://medicalxpress.com/news/2018-11-high-school-football-teenage-brain.html

Researchers find inhibiting one protein destroys toxic clumps seen in Parkinson's disease

November 14, 2018, Georgetown University Medical Center

Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

A defining feature of Parkinson's disease is the clumps of alpha-synuclein protein that accumulate in the brain's motor control area, destroying dopamine-producing neurons. Natural processes can't clear these clusters, known as Lewy bodies, and no one has demonstrated how to stop the build up as well as breakdown of the clumps—until perhaps now.

A team of neurologists at Georgetown University Medical Center (GUMC) has found through studies in mice and human brains, that one reason Lewy bodies develop is that a molecule, USP13, has removed all the "tags" placed on alpha-synuclein that mark the protein for destruction. Toxic heaps of alpha-synuclein accumulate, and are never taken away.

The findings, published in Human Molecular Genetics, show that inhibiting USP13 in mouse models of Parkinson's disease both eliminated Lewy bodies and stopped them from building up again. The "tag" that USP13 removes is called ubiquitin, which labels alpha-synuclein for degradation.

"This study provides novel evidence that USP13 affects development and clearance of Lewy body protein clumps, suggesting that targeting USP13 may be a therapeutic target in Parkinson's disease and other similar forms of neurodegeneration," says the study's lead investigator, Xiaoguang Liu, MD, Ph.D., an assistant professor of neurology.

There are three forms of motor disorders associated with build-up of alpha-synuclein. These "synucleinopathies" include Parkinson's, dementia with Lewy bodies, and multiple system atrophy.

Parkin is one of a family of ubiquitin ligase enzymes. Ubiquitination is a process in which molecules are labeled (or tagged) with ubiquitin and directed to cellular machines that break them down. USP13 is known as a de-ubiquitinating enzyme, which removes ubiquitin tags from protein. USP13 renders parkin ineffective via removal of ubiquitin tags (de-ubiquitination) from proteins. Loss of parkin function leads to genetically inherited forms of Parkinson's disease.

The study began with postmortem autopsies of individuals who donated their brains to research including 11 with Parkinson's disease and a control group of 9 without Parkinson's. The autopsies, which occurred 4 to 12 hours after death, found that the level of USP13 was significantly increased in the midbrain in Parkinson's disease patients, compared to the control participants.

"Overexpression of USP13 in post-mortem brains with Parkinson's disease was never discovered before this work. Its presence indicates that this molecule might reduce parkin's ability to tag proteins with ubiquitin or may strip ubiquitin away from certain molecules like alpha-synuclein, resulting in accumulation of toxic clumps in the brain," said Charbel Moussa, MBBS, Ph.D., the study senior investigator and director of GUMC Translational Neurotherapeutics Program.

Studies in mouse models of Parkinson's disease then demonstrated that knocking out the USP13 gene increased alpha-synuclein ubiquitination and destruction. Researchers also saw that USP13 knockdown protected the mice against alpha-synuclein-induced dopamine neuron death. The mice had improved motor performance; parkin protein was increased and alpha-synuclein was cleared.

Investigators also found that a newer therapy being studied in those with Parkinson's disease, nilotinib, worked better when USP13 was inhibited. Nilotinib is FDA approved for use in specific blood cancers.

"Our discovery clearly indicates that inhibition of USP13 is a strategic step to activate parkin and counteract alpha-synuclein de-ubiquitination, to increase toxic protein clearance" added Moussa. "Our next step is to develop a small molecule inhibitor of USP13 to be used in combination with nilotinib in order to maximize protein clearance in Parkinson's and other neurodegenerative diseases."

"To our knowledge, these data are the first to elucidate the role of USP13 in neurodegeneration," Liu says, suggesting that other neurodegeneration disorders that features protein clumps, such as Alzheimer's disease, may have a similar pathology.

"Clearance of neurotoxic proteins, including alpha-synuclein, may depend on the balance between ubiquitination and de-ubiquitinating," she says.

Journal reference: Human Molecular Genetics 

Provided by: Georgetown University Medical Center 

https://medicalxpress.com/news/2018-11-inhibiting-protein-toxic-clumps-parkinson.html

New advanced biomaterial to repair damaged nervous tissue

November 14, 2018, Universidad Politécnica de Madrid

Fluorescence microscopy images showing stem cells (green) implanted in a brain tissue (blue). The four figures at the right show the survival of non-encapsulated stem cells, and the figures at the right show the silk fibroin hydrogels-encapsulated stem cells. Credit: Front Cell Neurosci. 2018 Sep 6;12:296. doi: 10.3389/fncel.2018.00296

A team of researchers from the Centre for Biomedical Technology (CTB) at Universidad Politécnica de Madrid (UPM) in collaboration with the Universidad Complutense de Madrid (UCM), the Instituto Cajal and the Hospital Clínico San Carlos has developed an innovative treatment to repair damaged brain tissues. Thanks to the implantation of encapsulated stem cells in an innocuous biomaterial and fully biocompatible (silk fibroin), researchers have achieved the functional recovery of mice after suffering an induced brain stroke.

This encapsulation can increase the survival rate of stem cells implanted in the brain and, in addition to positively influencing the repair of damaged nerve tissue, it can prevent the extent of the damage.

A wide range of neurological disorders can cause permanent physical and cognitive disabilities. The nervous system has a limited capacity to recover after an injury, for instance after a stroke or brain trauma but also in neurodegenerative diseases such as Alzheimer's or Parkinson's in which there is a progressive deterioration of our brain.

Stem cell therapies have the therapeutic potential to protect and repair the damaged brain. However, transplanted stem cells has difficulties, including a reduced survival rate in the brain after transplant. This a barrier to achieving the most suitable therapy.

In order to overcome this barrier, a team led by researchers from the Centre for Biomedical Technology, in collaboration with UCM, the Instituto Cajal and the Hospital Clínico San Carlos, has developed an innovative bioengineering strategy to repair the damaged brain tissue. To do this, the researchers implanted mesenchymal stem cells encapsulated in fully biocompatible silk fibroin into mice with brain infarctions.

After the treatment, the mice experienced a significant improvement in their sensory and motor skills. Additionally, by using electrophysiological techniques, the researchers have shown improvement of brain reorganization in adjacent areas to the damaged zone. Silk fibroin considerably increased the survival of stem cells implanted in the brain, preventing an extent of the damage after de induced stroke in animals.

Daniel González Nieto, a CTB-UPM researcher, says, "These results are a step forward in new treatments of neurologic disorders when using silk fibroin as a drug delivery vehicle, achieving a higher therapy performance and the functional improvement of patients."

More information: Laura Fernández-García et al. Cortical Reshaping and Functional Recovery Induced by Silk Fibroin Hydrogels-Encapsulated Stem Cells Implanted in Stroke Animals, Frontiers in Cellular Neuroscience(2018). DOI: 10.3389/fncel.2018.00296 

Provided by: Universidad Politécnica de Madrid 

https://medicalxpress.com/news/2018-11-advanced-biomaterial-nervous-tissue.html