Posts tagged neurodegenerative diseases
Articles and news from the latest research reports.
Prion protein hints at role in aiding learning and memory
Research has found that prion helps our brains to absorb zinc, which is believed to be crucial to our ability to learn and the wellbeing of our memory.
The findings published in Nature Communications show that prion protein regulates the amount of zinc in the brain by helping cells absorb it through channels in the cell surface. It is already known that high levels of zinc between brain cells are linked with diseases such as Alzheimer’s and Parkinson’s.
Professor Nigel Hooper from the University’s Faculty of Biological Sciences explains: “With ageing, the level of prion protein in our brains falls and less zinc is absorbed by brain cells, which could explain why our memory and learning capabilities change as we get older. By studying both their roles in the body, we hope to uncover exactly how prion and zinc affect memory and learning. This could help us better understand how to maintain healthy brain cells and limit the effects of ageing on the brain.”
Whilst the abnormal infectious form of prion - which causes Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE) in cattle - has been extensively studied, the Leeds team is among the first to investigate the role of the ‘normal’ form of the protein.
Lead researcher, Dr Nicole Watts, says: “Zinc is thought to aid signalling in the brain as it’s released into the space between brain cells. However, when there’s too much zinc between the brain cells it can become toxic. High levels of zinc in this area between the brain cells are known to be a factor in neurodegenerative diseases, so regulating the amount of absorption by the cells is crucial.”
The research, funded by the Medical Research Council, Wellcome Trust and Alzheimer’s Research UK, may have implications for how we treat - and possibly prevent - neurodegenerative diseases in the future.
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, said: “We’re pleased to have helped support this study, which has uncovered new information that could one day aid the development of new treatments for Alzheimer’s. One next step would be to understand how regulating zinc levels may affect the progress of the disease. Results like these have the potential to lead to new and effective treatments - but for that to happen, we must build on these results and continue investing in research.”
(Source: fbs.leeds.ac.uk)
An immunosuppressive drug could delay the onset of neurodegenerative diseases
Rapamycin, a drug used to prevent rejection in transplants, could delay the onset of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. This is the main conclusion of a study published in the Nature in which has collaborated the researcher Isidro Ferrer, head of the group of Neuropathology at the Bellvitge Biomedical Research Institute (IDIBELL) and the Bellvitge University Hospital and Full Professor of Pathological Anatomy at the University of Barcelona. The research was led by researchers from the International School for Advanced Studies (SISSA) in Trieste (Italy).
The collaboration of the research group led by Dr. Ferrer with SISSA researchers began five years ago when they observed that Parkinson’s patients showed a deficit in UCHL1 protein. At that time, researchers didn’t know what mechanism produced this deficit. To discover it a European project was launched. It was coordinated by the Italian researchers and participated by other European research groups, including the group led by Dr. Ferrer. The project, called Dopaminet, focused on how dopaminergic neurons (brain cells whose neurotransmitter is dopamine) are involved in Parkinson’s disease.
Contrary to most common hypothesis that a DNA fragment encodes a protein through a messenger RNA molecule, the researchers found that it also works in reverse. They found a balance between the protein and its mirror protein, which is configured in reverse, and they are mutually controlled. If the protein mirror is located in the nucleus of the cell, it does not interact with the protein, while if it is in the cytoplasm, then both of them interact.
In the case of Parkinson’s disease the protein UCHL1 appears reduced and also its mirror protein is localized in the nucleus, and in the cytoplasm. Thus, the researchers sought a method to extract the mirror protein from the nucleus and made it interact with the original UCHL1 protein. The authors found that rapamycin was able to extract them from the nucleus. The drug allows the two proteins, the UCHL1 and its mirror, hold together in the cytoplasm, which would correct the mistakes that occur in Parkinson’s disease.
This in vitro research has allowed describing a new unknown mechanism. It is necessary that the UCHL1 mirror protein should accumulate in the nucleus and escape from the cytoplasm and join the UCLH1 protein. The combination of both makes the system work.
"The rapamycin can not cure Parkinson’s disease, but it may delay the onset of neurodegenerative diseases such as Alzheimer’s and Parkinson’s itself. Rapamycin can protect and delay the beginning of these diseases. It can complete the treatment, but it should be combined with other existing treatments", explains Isidro Ferrer.
Anyway, it is still far its application in patients. The next step is to validate these results in animal models and study the effects of rapamycin in combination with other drugs.
(Source: idibell.cat)
Neural-Like Stem Cells From Muscle Tissue May Hold Key to Cell Therapies for Neurodegenerative Diseases
Scientists at Wake Forest Baptist Medical Center have taken the first steps to create neural-like stem cells from muscle tissue in animals. Details of the work are published in two complementary studies published in the September online issues of the journals Experimental Cell Research and Stem Cell Research.
“Reversing brain degeneration and trauma lesions will depend on cell therapy, but we can’t harvest neural stem cells from the brain or spinal cord without harming the donor,” said Osvaldo Delbono, M.D., Ph.D., professor of internal medicine at Wake Forest Baptist and lead author of the studies.
“Skeletal muscle tissue, which makes up 50 percent of the body, is easily accessible and biopsies of muscle are relatively harmless to the donor, so we think it may be an alternative source of neural-like cells that potentially could be used to treat brain or spinal cord injury, neurodegenerative disorders, brain tumors and other diseases, although more studies are needed.”
In an earlier study, the Wake Forest Baptist team isolated neural precursor cells derived from skeletal muscle of adult transgenic mice (PLOS One, Feb.3, 2011).
In the current research, the team isolated neural precursor cells from in vitro adult skeletal muscle of various species including non-human primates and aging mice, and showed that these cells not only survived in the brain, but also migrated to the area of the brain where neural stem cells originate.
Another issue the researchers investigated was whether these neural-like cells would form tumors, a characteristic of many types of stem cells. To test this, the team injected the cells below the skin and in the brains of mice, and after one month, no tumors were found.
“Right now, patients with glioblastomas or other brain tumors have very poor outcomes and relatively few treatment options,” said Alexander Birbrair, a doctoral student in Delbono’s lab and first author of these studies. “Because our cells survived and migrated in the brain, we may be able to use them as drug-delivery vehicles in the future, not only for brain tumors but also for other central nervous system diseases.”
In addition, the Wake Forest Baptist team is now conducting research to determine if these neural-like cells also have the capability to become functioning neurons in the central nervous system.
(Source: newswise.com)
Transplantation of Embryonic Neurons Raises Hope for Treating Brain Diseases
The unexpected survival of embryonic neurons transplanted into the brains of newborn mice in a series of experiments at the University of California, San Francisco (UCSF) raises hope for the possibility of using neuronal transplantation to treat diseases like Alzheimer’s, epilepsy, Huntington’s, Parkinson’s and schizophrenia.
The experiments, described this week in the journal Nature, were not designed to test whether embryonic neuron transplants could effectively treat any specific disease. But they provide a proof-of-principle that GABA-secreting interneurons, a type of brain cell linked to many different neurological disorders, can be added in significant numbers into the brain and can survive without affecting the population of endogenous interneurons.
The survival of these cells after transplantation in numbers far greater than expected came as a shock to the team, which was led by UCSF professor Arturo Alvarez-Buylla, PhD, and former UCSF graduate student Derek Southwell, MD, PhD.
The prevailing theory held that the survival of developing neurons is something like a game of musical chairs. The brain has limited capacity for these cells, forcing them to compete with each other for the few available slots. Only those that find a place to “sit” (and receive survival signals derived from other cell types) will survive when the music stops. The rest die a withering death.
Study gives clues to causes of Motor Neurone Disease
Scientists at the University of Bath are one step further to understanding the role of one of the proteins that causes the neurodegenerative disorder, Amyotrophic Lateral Sclerosis (ALS), also known as Motor Neurone Disease (MND).
The scientists studied a protein called angiogenin, which is present in the spinal cord and brain that protects neurones from cell death. Mutations in this protein have been found in sufferers of MND and are thought to play a key role in the progression of the condition.
MND triggers progressive weakness, muscle atrophy and muscle twitches and spasms. The disease affects around 5000 people in the UK.
The team of cell biologists and structural biologists have, for the first time, produced images of the 3D structures of 11 mutant versions of angiogenin to see how the mutations changed the structure of the active part of the molecule, damaging its function.
The study, published in the prestigious journal Nature Communications, provides insights into the causes of this disease and related conditions such as Parkinson’s Disease.
The team also looked at the effects of the malfunctioning proteins on neurones grown from embryonic stem cells in the laboratory.
They found that some of the mutations stopped the protein being transported to the cell nucleus, a process that is critical for the protein to function correctly.
The mutations also prevented the cells from producing stress granules, the neurone’s natural defence from stress caused by low oxygen levels.
Dr Vasanta Subramanian, Reader in Biology & Biochemistry at the University, said:
“This study is exciting because it’s the first time we’ve directly linked the structure of these faulty proteins with their effects in the cell.
“We’ve worked alongside Professor Ravi Acharya’s group to combine structural knowledge with cell biology to gain new insights into the causes of this devastating disease.
“We hope that the scientific community can use this new knowledge to help design new drugs that will bind selectively to the defective protein to protect the body from its damaging effects.”
The findings were welcomed by medical research charity, the Motor Neurone Disease (MND) Association, the only national charity in England, Wales and Northern Ireland dedicated to supporting people living with MND while funding and promoting cutting-edge global research to bring about a world free of the disease.
Dr Brian Dickie, Director of Research Development at the charity, said: “The researchers at the University of Bath have skilfully combined aspects of biology, chemistry and physics to answer some fundamental questions on how angiogenin can damage motor neurones. It not only advances our understanding of the disease, but may also give rise to new ideas on treatment development.”
(Source: bath.ac.uk)
Gladstone Scientists Identify Biological Mechanism that Plays Key Role in Early-Onset Dementia: Findings explain how protein deficiency contributes to neurodegenerative disease
Using animal models, scientists at the Gladstone Institutes have discovered how a protein deficiency may be linked to frontotemporal dementia (FTD)—a form of early-onset dementia that is similar to Alzheimer’s disease. These results lay the foundation for therapies that one day may benefit those who suffer from this and related diseases that wreak havoc on the brain.
As its name implies, FTD is a fatal disease that destroys cells, or neurons, that comprise the frontal and temporal lobes of the brain—as opposed to Alzheimer’s which mainly affects brain’s memory centers in the hippocampus. Early symptoms of FTD include personality changes, such as increased erratic or compulsive behavior. Patients later experience difficulties speaking and reading, and often suffer from long-term memory loss. FTD is usually diagnosed between the ages of 40 and 65, with death occurring within 2 to 10 years after diagnosis. No drug exists to slow, halt or reverse the progression of FTD.
A new study led by Gladstone Senior Investigator Robert V. Farese, Jr., MD, offers new hope in the fight against this and other related conditions. In the latest issue of the Journal of Clinical Investigation, Dr. Farese and his team show how a protein called progranulin prevents a class of cells called microglia from becoming “hyperactive.” Without adequate progranulin to keep microglia in check, this hyperactivity becomes toxic, causing abnormally prolonged inflammation that destroys neurons over time—and leads to debilitating symptoms.
Researchers have discovered a way to generate new human neurons from another type of adult cell found in our brains. The discovery, reported in the October 5th issue of Cell Stem Cell, a Cell Press publication, is one step toward cell-based therapies for the treatment of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s.
Potential new class of drugs blocks nerve cell death
Diseases that progressively destroy nerve cells in the brain or spinal cord, such as Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), are devastating conditions with no cures.
Now, a team that includes a University of Iowa researcher has identified a new class of small molecules, called the P7C3 series, which block cell death in animal models of these forms of neurodegenerative disease. The P7C3 series could be a starting point for developing drugs that might help treat patients with these diseases. These findings are reported in two new studies published the week of Oct. 1 in the online early edition of the Proceedings of the National Academy of Sciences (PNAS).
“We believe that our strategy for identifying and testing these molecules in animal models of disease gives us a rational way to develop a new class of neuroprotective drugs, for which there is a great, unmet need,” says Andrew Pieper, M.D., Ph.D., associate professor of psychiatry at the UI Carver College of Medicine, and senior author of the two studies.
About six years ago, Pieper, then at the University of Texas Southwestern Medical Center, and his colleagues screened thousands of compounds in living mice in search of small, drug-like molecules that could boost production of neurons in a region of the brain called the hippocampus. They found one compound that appeared to be particularly successful and called it P7C3.
“We were interested in the hippocampus because new neurons are born there every day. But, this neurogenesis is dampened by certain diseases and also by normal aging,” Pieper explains. “We were looking for small drug-like molecules that might enhance production of new neurons and help maintain proper functioning in the hippocampus.”
However, when the researchers looked more closely at P7C3, they found that it worked by protecting the newborn neurons from cell death. That finding prompted them to ask whether P7C3 might also protect existing, mature neurons in other regions of the nervous system from dying as well, as occurs in neurodegenerative disease.
Using mouse and worm models of PD and a mouse model of ALS, the research team has now shown that P7C3 and a related, more active compound, P7C3A20, do in fact potently protect the neurons that normally are destroyed by these diseases. Their studies also showed that protection of the neurons correlates with improvement of some disease symptoms, including maintaining normal movement in PD worms, and coordination and strength in ALS mice.
(Source: now.uiowa.edu)
Fly neurons could reveal the root of Alzheimer’s disease, says a TAU researcher
Ya’ara Saad, a PhD candidate in the lab of Prof. Amir Ayali at TAU’s Department of Zoology and the Sagol School of Neurosciences. is exploring how neural networks develop one neuron at a time. In the lab, the researchers break the fly’s nervous system down into single cells, separate these cells, then place them at a distance from each other in a Petri dish. After a few days, the neurons begin to grow towards one another and establish connections, and then migrate to form clusters of cells. Finally, they re-organize themselves to form a sophisticated network, says Saad. Because these experiments uniquely allow researchers to concentrate on individual neurons, they can perform specific measurements of proteins, note electrical activity, watch synapses develop, and see how physical changes take shape.
Saad and her fellow researchers are using this technique to observe how neurodegenerative diseases take over the neurons and to potentially test various medicinal interventions. In their experiments, one group of flies is genetically modified so that it expresses a peptide called Amyloid Beta, found in protein-based plaques of human Alzheimer’s disease patients. The results of these studies are then compared to those of a non-modified control group. Both strains of flies are provided by Prof. Daniel Segal of TAU’s Department of Molecular Microbiology and Biotechnology.
Previous studies performed on flies expressing Amyloid Beta showed that they demonstrate Alzheimer’s-like symptoms such as motor problems, impaired learning capabilities, and shorter lifespans. While this peptide has been researched for quite some time, scientists still do not know how it functions. Saad says her work may help unlock the mystery of this function. “Now I can really get into the molecular operation of Amyloid Beta inside the cell. I can watch the dysfunction in the synapses, monitor the proteins involved, and record electrical activity in a much more accessible way,” she says.
Kansas State University researchers have discovered a molecule that may be capable of delivering drugs inside the body to treat diseases.
For the first time, researchers have designed and created a membrane-bounded vesicle formed entirely of peptides — molecules made up of amino acids, the building blocks of protein. The membrane could serve as a new drug delivery system to safely treat cancer and neurodegenerative diseases.
A study led by John Tomich, professor of biochemistry at Kansas State University, has been published in the journal PLOS ONE in September, and a patent for the discovery is pending.
(Source: k-state.edu)