Monthly Archives: Maj 2017

A simple blood test may be as accurate as a spinal fluid test when trying to determine whether symptoms are caused by Parkinson’s disease or another atypical parkinsonism disorder, according to a new study published in Neurology.

In early stages of disease, it can be difficult to differentiate between Parkinson’s disease and atypical parkinsonism disorders (APDs) like multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, because symptoms can overlap. But identifying these diseases early is important because expectations concerning progression and potential benefit from treatment differ dramatically between Parkinson’s and APDs.

The study found that a nerve protein called neurofilament light chain protein can, when found in the blood, discriminate between Parkinson’s disease and APDs . It is a component of nerve cells and can be detected in the blood stream and spinal fluid when nerve cells die.

For the study, researchers examined 504 people from three study groups. Two groups, had healthy people and people who had been living with Parkinson’s or APDs for an average of four to six years. The third group was comprised of people who had been living with the diseases for three years or less. In all, there were 244 people with Parkinson’s, 88 with multiple system atrophy, 70 with progressive supranuclear palsy, 23 with corticobasal degeneration and 79 people who served as healthy controls.

Researchers found the blood test was just as accurate as a spinal fluid test at diagnosing whether someone had Parkinson’s or an APD, in both early stages of disease and in those who had been living with the diseases longer. The nerve protein levels were higher in people with APDs and lower in those with Parkinson’s disease and those who were healthy.

The researchers say that one limitation of nerve protein testing is that it does not distinguish between the different APDs, however, they note that doctors can look for other symptoms and signs to distinguish between those diseases.

Paper: “Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder”
Reprinted from materials provided by the American Academy of Neurology (AAN).

Scientists say neurodegenerative diseases like Alzheimer’s and Parkinson’s may be linked to defective brain cells disposing toxic proteins that make neighboring cells sick.

In a study published in Nature, researchers found that while healthy neurons should be able to sort out and rid brain cells of toxic proteins and damaged cell structures without causing problems, laboratory findings indicate that it does not always occur.

These findings could have major implications for neurological disease in humans and possibly be the way that disease can spread in the brain.

Scientists have understood how the process of eliminating toxic cellular substances works internally within the cell, comparing it to a garbage disposal getting rid of waste, but they did not know how cells released the garbage externally.

Working with the transparent roundworm, known as the C. elegans, which are similar in molecular form, function and genetics to those of humans, the researchers discovered that the worms — which have a lifespan of about three weeks — had an external garbage removal mechanism and were disposing these toxic proteins outside the cell as well.

The researchers found that roundworms engineered to produce human disease proteins associated with Huntington’s disease and Alzheimer’s, threw out more trash consisting of these neurodegenerative toxic materials. While neighboring cells degraded some of the material, more distant cells scavenged other portions of the diseased proteins.

Paper: “C. elegans neurons jettison protein aggregates and mitochondria under neurotoxic stress”
Reprinted from materials provided by Rutgers University.

A team of researchers has identified an underlying mechanism in early onset Parkinson’s. Using flies, mice and patient cells, the team focused on cardiolipin, a fat unique to cells’ mitochondria, organelles that produce energy. They demonstrated that reducing the effects of the protein FASN influences the mitochondria, leading to increased cardiolipin levels and reduced Parkinson’s symptoms. These results could pave the way to therapies for Parkinson’s disease that target lipids. The research was published in The Journal of Cell Biology.

An estimated 10 million people are currently affected by Parkinson’s disease worldwide. A small percentage gets confronted with the disease before the age of 40. While the causes are not yet known, scientists believe that they consist of both genetic and environmental factors. In genetic Parkinson’s disease, a mutation in the PINK1 gene causes changes in neurons’ mitochondria, leading to the degeneration of these neurons.

In this study, scientists used fly, mouse and human cell models to observe that blocking a protein called FASN, which is responsible for lipid creation in cells, bypasses the genetic defect in mitochondria.

The researchers have already identified several targets for future research projects seeking greater insights into the link between the amounts of specific lipids in neurons and Parkinson’s disease.

Paper: “Cardiolipin promotes electron transport between ubiquinone and complex I to rescue PINK1 deficiency”
Reprinted from materials provided by VIB – Flanders Interuniversity Institute for Biotechnology.

An international group of researchers has identified new processes that form protein “clumps” that are characteristic of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). How these proteins, which can bind RNA in normal cells, stick together has remained elusive until recently, when scientists demonstrated that they demix from the watery substance inside cells, much like oil separates from water. This latest research, featured on the cover of Molecular Cell, sheds light onto the molecular interactions behind the process in patients with defects in the C9orf72 gene.

Clumps of RNA-binding proteins occur naturally in normal neurons under times of stress in the form of stress granules (SGs), which precipitate from the water inside cells. However, in normal cells, the process of stress granule formation is tightly controlled, reversible and does not lead to disease. Scientists previously believed that hydrophobic interactions – or the protein’s inability to mix with water – caused the formation of stress granules. However, the researchers showed that in patients with defects in the C9orf72 gene, a different process can also cause this demixing, which precedes the formation of these toxic protein aggregates.

Stress granules normally behave as liquid protein droplets within a cell, while protein aggregates do not. The C9orf72 mutation causes neurons to produce small, abnormal and highly charged toxic proteins, or peptides. Yet, precisely how these peptides are toxic was not well-understood. The research team was able to observe in vitro that these peptides cause RNA-binding proteins to spontaneously stick together and change the dynamics of stress granules in cells, making them more like solids than liquids.

The scientists suggest that future research could focus on the development of a sort of ‘molecular antifreeze’ to prevent solidification and, thus, protein aggregation.

Paper: “Phase Separation of C9orf72 Dipeptide Repeats Perturbs Stress Granule Dynamics”
Reprinted from materials provided by VIB – Flanders Interuniversity Institute for Biotechnology.

For the first time a “tipping point” molecular link between the blood sugar glucose and Alzheimer’s disease has been established by scientists, who have shown that excess glucose damages a vital enzyme involved with inflammation response to the early stages of Alzheimer’s.

The study was published in Scientific Reports.

Abnormally high blood sugar levels, or hyperglycaemia, is well-known as a characteristic of diabetes and obesity, but its link to Alzheimer’s disease is less familiar.
Diabetes patients have an increased risk of developing Alzheimer’s disease compared to healthy individuals. In Alzheimer’s disease abnormal proteins aggregate to form plaques and tangles in the brain which progressively damage the brain and lead to severe cognitive decline.

Scientists already knew that glucose and its break-down products can damage proteins in cells via a reaction called glycation but the specific molecular link between glucose and Alzheimer’s was not understood.

But now scientists have unraveled that link. By studying brain samples from people with and without Alzheimer’s using a sensitive technique to detect glycation, the team discovered that in the early stages of Alzheimer’s glycation damages an enzyme called MIF (macrophage migration inhibitory factor) which plays a role in immune response and insulin regulation.

MIF is involved in the response of brain cells called glia to the build-up of abnormal proteins in the brain during Alzheimer’s disease, and the researchers believe that inhibition and reduction of MIF activity caused by glycation could be the ‘tipping point’ in disease progression. It appears that as Alzheimer’s progresses, glycation of these enzymes increases.

Paper: “Macrophage Migration Inhibitory Factor is subjected to glucose modification and oxidation in Alzheimer’s Disease”
Reprinted from materials provided by University of Bath.