Researchers are optimistic about developing a new therapy for sufferers of neurodegenerative brain disorders.
Vast amounts of financial resources and scientific discovery has gone into understanding the intricate processes that lead to neurodegenerative brain disorders, such as Parkinson’s, Alzheimer’s, and Huntington’s.
What is known thus far is that over a period of time, the structure and function of certain brain cells deteriorate, leading ultimately to neuron death. Neuron death is implicated in the onset of progressive brain disorders such as Alzheimer’s.
A Mutated Gene Impacts Brain Cell Health
Previous studies identified a causal relationship between the UBQLN2 gene and neuron degeneration.
It was found that when the UBQLN2 gene mutates, it contributes in some way to neuron degeneration.
However, the key to unlocking the dynamics of the relationship was still missing.
A recent study out of the University of Glasgow, “UBQLN2 Mediates Autophagy-Independent Protein Aggregate Clearance by the Proteasome”, seems to give an exciting new clue into this dynamic interplay between the gene and neuron impairment.
Researchers discovered that healthy UBQLN2 genes have a vital function to fulfill in maintaining neuron health. In mouse models, the undamaged UBQLN2 gene helped to remove toxic protein clumps which form in brain cells.
It is known that these protein clumps cause neurodegeneration. However, when the UBQLN2 gene is mutated, it ceases to serve this vital function and the protein clumps proliferate.
Glasgow’s Dr. Thimo Kurz, PhD from the Institute of Molecular, Cell, and Systems Biology, said that patients with a neurological disease show significant clumps in their brain cells.
When mimicking Huntington’s disease in mice models, it was discovered that the mutated UBQLN2 gene did not serve its function of cleaning the neurons of these protein clumps.
Dr. Roland Hjerpe, the study’s author, noted that the study’s significance extends beyond the role of UBQLN2 in dementia. He looks forward to the development of new therapeutic models that will treat a broad range of neurodegenerative diseases.
An interdisciplinary team comprised of scientists and engineers at Northwestern University has developed a new non-invasive technique for the detection of Alzheimer's in animals. The team used MRI to detect traces of the disease at very early stages.
The MRI probe which the scientists developed is able to link the magnetic nanostructure with antibodies that locate the amyloid beta toxins in the brain. The toxins are responsible for Alzheimer's and the proteins can be identified as darker areas on an MRI scan of the brain. Being able to identify molecular toxins in animals may allow researchers to develop methods to detect early signs by rendering the toxins incapable of causing more damage. Although this wasn't the intended area of study, the researchers will hopefully be able to design treatment plans and ways to eliminate toxins while improving patient health.
These findings are a diversion from the conventional methods by identifying toxin amyloid oligomers rather than plaques, known for developing later in cases of Alzheimer's disease. Furthermore, the oligomers are acknowledged as the culprit for the onset of the disease and related memory loss.
Being able to identify oligomers is a huge breakthrough, as they are often present for anywhere up to 10 years in the brain before the plaques they form can be detected. Detecting amyloid beta oligomers is critical for two main reasons: firstly the oligomers are toxins responsible for damaging neurons, and secondly, oligomers are the earliest precursor for Alzheimer's.
Researchers used mice with Alzheimer's and delivered the probe intranasally to the animals with the disease and a control group without it. In those with Alzheimer's, these toxins were positively identified through the MRI scans, while no signs were present in the control group. Following a single MRI probe researchers witnessed an improvement in animal behavior. Brain tissue of humans was also tested and showed dark areas, indicating a presence of the oligomers.
Researchers originally focused on iron due to its links to Alzheimer's and Parkinson's disease. As the nematode C. elegans aged, levels of copper, iron, manganese and calcium increased. Researchers then discovered that iron accumulated at a much greater rate than the other metals. They altered the nematode's diet and found that four day old nematodes that were fed iron for two days resembled fifteen day-old nematodes. It's believed that the iron was the accelerator in their rapid aging process.
Researchers expected to find changes due to oxidative stress, however they actually witnessed a normal aging process. Iron created dysfunction and the build-up of proteins. This is typical of the aging process, so scientists believe that the iron was driving aging.
In addition the scientists also tested the nematodes with CaEDTA; a metal chelator typically associated with treatment of people at risk from lead poisoning. The chelator reduced the age-related build-up of iron, and increased the lifespan of the nematodes. CaDETA also shielded nematodes that were genetically bred to produce protein aggregations associated with human diseases.
Dr Lithgow was the lead author of the study. He concluded that maintaining a proper balance of metals is essential to good health, while it's also apparent that the precious balance can be upset with age. He stressed that the phenomenon has yet to be extensively studied and that this is an exciting area for future exploration.
Epilepsy drug reduces brain hyperactivity
One of the causes of epilepsy is too much activity in the brain. Levetiracetam is an antiepileptic drug that quiets the brain and reduces seizures. It was already established that amnestic mild cognitive impairment (aMCI) is caused by too much activity in the hippocampal region of the brain. aMCI results in memory loss earlier in life than is normal and at a much more significant degree. Additionally, aMCI has proven to be a good determiner of developing Alzheimer’s. The researchers at Johns Hopkins sought to know if the drug that calms brain activity for epileptics could be used to stem cognitive dysfunction.
Memory was improved with levetiracetam
Researchers administered varied dosages to a study group of 84 subjects. Sixty-seven already had symptoms of memory loss and the remainder were in the control group. A placebo was also administered. As subjects undertook specially designed tasks, MRI scans measured brain activity. It was proven that low dosages of levetiracetam not only quieted hyperactivity in the hippocampal region, but also that cognitive tasks were easier to accomplish. It was a very encouraging outcome, offering a glimmer of hope that memory loss can be treated through levetiracetam.
Further studies required
Researchers must discover if administration of levetiracetam over the long-term can stop decline in cognitive abilities, or if it can save a person from developing Alzheimer’s.
New Study Confirms: Klotho allele gene plays pivotal role in cognitive functioning in middle-age and older citizens