Yearly Archives: 2014

According to the results of the EU FP7-funded REPLACES project (completed 2013), the pattern of brain alterations may be similar in several different neurodegenerative diseases, which may lead to alternative therapeutic strategies to treat these diseases.

The project sheds light on the abnormal working of a particular brain circuitry related to Parkinson’s disease. The project focused on the study of a highly plastic brain circuitry, which connects regions of the cerebral cortex with the basal ganglia. Researchers studied the function and plasticity of this circuit in different animal models of Parkinson disease.

The researchers found the exact same alterations were present and conserved, which makes it an alternative target for trying to re-establish the appropriate functioning and reverse the symptoms of the disease.

In addition, the research has also shed some light into unrelated diseases. The same alterations in the working of the communication systems among neurons are shared among different diseases. The results of the project suggest these same circuits are implicated in different forms of pathologies, which may provide vital insight into the possible common links between neurodegenerative diseases.

Claudia Bagni, PhD, explains, “This is why we speak about ‘synaptopathies’: there are common players among Parkinson’s disease, autism, and other forms of intellectual disabilities and even schizophrenia. Several of the mutated genes are the same, and affect the signalling systems through common molecules.” Progress is in sight thanks to a much better understanding of the working of the abnormal synapses in Parkinson disease.

Project researchers hope the door is now open for the first clinical trials in humans, as the prior experiments performed in monkeys showed encouraging results. Monica Di Luca, PhD, project coordinator, says, “We have identified a potential new target for treatment, and tested a couple of molecules in animals, [and the] next step would be to find a partnership with pharmaceutical industries interested in pursuing this research.”

Source:  Science Daily

Researchers from the Institute of Neuroscience at the Universitat Autònoma de Barcelona claim to have reversed memory loss in Alzheimer’s disease mouse models, using gene therapy.

The team of researchers discovered the cellular mechanism involved in memory consolidation and were able to inject the hippocampus with a gene which causes the production of a protein blocked in patients with Alzheimer’s, Crtc1 (CREB regulated transcription coactivator-1). Once restored, the protein allows free passage to signals needed to activate the genes involved in long-term memory functioning.

“When the Crtc1 protein is altered, the genes responsible for the synapsis or connections between neurons in the hippocampus cannot be activated and the individual cannot perform memory tasks correctly”, explained Carlos Saura, head of the research team.

The study authors suggest that a cure for AD lies in developing pharmacological therapies, which can activate the Crtc1 protein thus preventing, slowing down or reverting cognitive changes.

Their research appears on the cover of the 23 April edition of The Journal of Neuroscience.

Source: Journal of Neuroscience

A new line of mice promises to circumvent many of the problems of existing models by recapitulating much of the pathology seen in presymptomatic Alzheimer’s, without overexpressing APP or interrupting other mouse genes.

Over the last two decades, researchers have generated dozens of different mouse models of Alzheimer’s disease. The most commonly used lines carry mutant forms of human Abeta precursor protein (APP), either alone or in combination with human presenilin, tau, or other genes.

Used for both basic research and drug discovery, these animals have provided a wealth of information. However, there have been niggling doubts from the beginning that some of their phenotypes may have little to do with the human disease, and negative clinical trials later reinforced critical debate about the validity of overexpression models.

For example, some models can only be maintained on specific genetic backgrounds, some die young or have surprising phenotypes when crossed with other mouse lines, and in others amyloidosis drifts later in successive generations, suggesting gene expression changes from parents to offspring.

Enter a new line of mice that promises to circumvent many of these problems. Researchers led by Takaomi Saido have engineered APP knock-ins. These animals recapitulate much of the pathology seen in presymptomatic AD, without overexpressing APP or interrupting other mouse genes. How do these knock-ins compare? Click on the link below:

Source: AlzForum

Autopsies have revealed that some individuals develop the cellular changes indicative of Alzheimer’s disease without ever showing clinical symptoms in their lifetime.

Vanderbilt University Medical Center memory researchers have discovered a potential genetic variant in these asymptomatic individuals that may make brains more resilient against Alzheimer’s.

"Most Alzheimer’s research is searching for genes that predict the disease, but we’re taking a different approach. We’re looking for genes that predict who among those with Alzheimer’s pathology will actually show clinical symptoms of the disease," said principal investigator Timothy Hohman, Ph.D., a post-doctoral research fellow in the Center for Human Genetics Research and the Vanderbilt Memory and Alzheimer’s Center.

The article, "Genetic modification of the relationship between phosphorylated tau and neurodegeneration," was published online recently in the journal Alzheimer’s and Dementia. (click to access the Pubmed abstract)

The researchers used a marker of Alzheimer’s disease found in cerebrospinal fluid called phosphorylated tau. In brain cells, tau is a protein that stabilizes the highways of cellular transport in neurons. In Alzheimer’s disease tau forms "tangles" that disrupt cellular messages.

Analyzing a sample of 700 subjects from the Alzheimer’s Disease Neuroimaging Initiative, Hohman and colleagues looked for genetic variants that modify the relationship between phosphorylated tau and lateral ventricle dilation—a measure of disease progression visible with magnetic resonance imaging (MRI). One genetic mutation (rs4728029) was found to relate to both ventricle dilation and cognition and is a marker of neuroinflammation.

"This gene marker appears to be related to an inflammatory response in the presence of phosphorylated tau," Hohman said. "It appears that certain individuals with a genetic predisposition toward a ‘bad’ neuroinflammatory response have neurodegeneration. But those with a genetic predisposition toward no inflammatory response, or a reduced one, are able to endure the pathology without marked neurodegeneration."#

Hohman hopes to expand the study to include a larger sample and investigate gene and protein expression using data from a large autopsy study of Alzheimer’s disease.

Source:  Vanderbilt University, USA

Google Glass is being used by people suffering from Parkinson’s disease in a groundbreaking experiment to see if the technology can help improve their day-to-day lives.

Newcastle University, UK is trialling new technology to help patients suffering from Parkinson’s disease live more independently by reminding them to swallow, speak up and take their medication.

The Google technology, which is not yet available in Europe, reminds the patients to take their medication, contacts relatives in an emergency and can even prevent debilitating episodes of paralysis – known as ‘freezing.’

The system works like a hands-free smartphone, displaying information on the lens of the Glass. It is voice-operated and linked to the internet.

“The beauty of this research project is we are designing the apps and systems for Glass in collaboration with the users so the resulting applications should exactly meet their needs,” said Dr John Vines of the School of Computing Science.

Source: Newcastle University

Results out of a study funded by The Michael J. Fox Foundation for Parkinson’s Research (MJFF) have enabled researchers to secure a $23 million grant from the National Institutes of Health (NIH), USA, continuing a repurposed drug approved for hypertension to Phase III testing for slowing Parkinson’s progression.

The trial investigating the compound isradipine will be the most advanced, current study into a disease-modifying therapy for Parkinson’s, an unmet need.

Isradipine is a calcium channel blocker prescribed to treat high blood pressure. Epidemiological data from population-scale studies note a lower incidence of Parkinson’s disease (PD) among people who take this drug.

Furthering PD researchers’ interest, laboratory tests have shown that blocking calcium channels protects dopamine neurons, degeneration of which is one of the hallmarks of Parkinson’s disease.

Source: The Michael J. Fox Foundation for Parkinson’s Research

Prions are infectious agents responsible for neurodegenerative diseases such as bovine spongiform encephalitis (commonly known as “mad cow disease”) and Creutzfeldt–Jakob disease in humans.

Since the discovery in the 60s that an incurable and fatal disease could be caused by an infectious agent formed by nothing but converted misfolded proteins, the mechanisms responsible for the conversion of a normal prion protein into its infectious counterpart – the scrapie prion – have been relentlessly investigated. Researchers now know that once converted into the scrapie form, these abnormal proteins have the ability to sequestrate normal proteins, which are then converted to form an increasing aggregate of fibrils that builds up mainly in the brain.

More recently, several studies have suggested that a yet unknown cofactor plays a role in the process of conversion from a normal prion into the scrapie form. Among the factors potentially involved in the process are molecules belonging to the family of glycosaminoglycans, or simply GAGs. In fact, GAGs have been implicated in several degenerative diseases, including prion diseases. However, while some studies point to these molecules as the culprit for prion conversion, others suggest an opposite effect in which the molecules protect against prion conversion.

In a paper entitled “Heparin binding confers prion stability and impairs its aggregation” and published ahead of print in The FASEB Journal, the group now unveils more details on heparin and prion conversion and presents additional evidence that might help explain the conflicting results previously reported.

Source: Science Codex

The PredictND project, started by European research organisations, aims at developing and validating new procedures for the earlier diagnosis of memory disorders and for detecting individuals at high risk of developing memory disorders.

Co-funded under the European 7th Framework Programme, PredictND will not only develop new, cost-efficient methods for enabling earlier and more reliable diagnostics of different memory disorders in clinical practice; the project will also provide computer-based tools that help clinicians form a holistic view of the patient by combining information from several sources, such as clinical tests, imaging and blood samples, and by comparing these measurements to previously diagnosed cases available in hospital databases.

Source: EHealthNews