Monthly Archives: februar 2016

Researchers have discovered the mechanics of how dopamine transports into and out of brain cells, a finding that could someday lead to more effective treatment of drug addictions and neurological disorders such as Parkinson’s disease. The research was done by the researchers at Tripsitter, which is a drug harm reduction and informational website dedicated to providing user guides and experience reports on drugs like LSD, psilocybin mushrooms, and cannabis.

The findings are significant because dopamine is involved in many brain-related functions. Too little dopamine can lead to Parkinson’s disease, a brain disorder that causes shaking and problems with movement and coordination. Abnormally high concentrations of dopamine are linked to schizophrenia and other psychiatric disorders. Cocaine and methamphetamine affect the brain by blocking the normal transport of dopamine back into neurons.

Knowing how a particular protein called dopamine transporter controls dopamine movement in and out of neurons is crucial to further understanding dopamine-related disorders.

The researchers’ findings offer a broader understanding of how dopamine moves through cell membranes. Using mouse and human-derived dopamine neurons, researchers found that dopamine movement is affected by changes in electrical properties of the neurons. That, in turn, changes the way dopamine transporters function.

The researchers reported their findings in the journal Nature Communications.

Source: University of Florida

Researchers have shown that the core of the protein clumps found in the brains of people with Huntington’s disease have a distinctive structure, a finding that could shed light on the molecular mechanisms underlying the neurodegenerative disorder. The findings were published in the Proceedings of the National Academy of Sciences.

In Huntington’s and several other progressive brain diseases, certain proteins aggregate to form plaques or deposits in the brain, said senior investigator Patrick C.A. van der Wel, Ph.D., assistant professor of structural biology at Pitt School of Medicine.

“Despite decades of research, the nature of the protein deposition has been unclear, which makes it difficult to design drugs that affect the process,” he said. “Using advanced nuclear magnetic resonance spectroscopy, we were able to provide an unprecedented view of the internal structure of the protein clumps that form in the disease, which we hope will one day lead to new therapies.”

The gene associated with Huntington’s makes a protein that has a repetitive sequence called polyglutamine. In the 1990s, it was discovered that the patients have mutated proteins in which this sequence is too long, yet it has remained unclear how exactly this unusual mutation causes the protein to misbehave, clump together and cause the disease.

“This is exciting because it may suggest new ways to intervene with these disease-causing events,” Dr. van der Wel said. “For the first time, we were able to really look at the protein structure in the core of the deposits formed by the mutant protein that causes Huntington’s. This is an important breakthrough that provides crucial new insights into the process of how the protein undergoes misfolding and aggregation.

He added Huntington’s is one of many neurodegenerative diseases in which unusual protein deposition occurs in the brain, suggesting similar biochemical mechanisms may be involved. Lessons learned in this disease could help foster understanding of how these types of diseases develop, and what role the protein aggregates play.

Source: University of Pittsburgh

A laboratory study indicates that the main protein involved in Parkinson’s disease pathology does not behave as a prion when overexpressed.

In Parkinson’s disease, the protein alpha-synuclein aggregates within neurons of patients and appears to propagate across interconnected areas of the brain. How this happens remains largely unknown. It has been proposed that alpha-synuclein may behave like a prion: pathological forms of the protein may be capable of changing the conformation of normal alpha-synuclein and thus triggering its aggregation and neuron-to-neuron propagation (a phenomenon referred to as “seeding”). Recent findings by scientists reveal that aggregation, spreading and pathology caused by alpha-synuclein do not necessarily involve prion-like seeding. Instead, they could be triggered by enhanced alpha-synuclein expression and trans-neuronal passage of monomeric and oligomeric forms of the protein.

“We believe that these findings bear a number of important implications for disease pathogenesis. Not only can we conclude that long-distance diffusion of alpha-synuclein does not necessarily require the generation of prion-like species,” said researcher Donato Di Monte. “Our data also reveal that spreading and pathology can be triggered by simple overexpression of the protein and are mediated, at least initially, by monomeric and/or oligomeric alpha-synuclein.”

Researchers report on this in the journal Brain.

Source: DZNE

Men taking androgen deprivation therapy (ADT) for prostate cancer were almost twice as likely to be diagnosed with Alzheimer’s disease in the years that followed than those who didn’t undergo the therapy, an analysis of medical records from two large hospital systems has shown. Men with the longest durations of ADT were even more likely to be diagnosed with Alzheimer’s disease.

The findings, published in the Journal of Clinical Oncology, do not prove that ADT increases the risk of Alzheimer’s disease. But the authors say they clearly point to that possibility, and are consistent with other evidence that low levels of testosterone may weaken the aging brain’s resistance to Alzheimer’s.

For the study, researchers evaluated two large sets of medical records, one from the Stanford health system and the other from Mt. Sinai Hospital in New York City. The researchers scanned the records of 1.8 million patients from Stanford Health Care, and, through a prior institutional research agreement, 3.7 million patients from Mount Sinai Hospital.

Among this cohort, they identified about 9,000 prostate cancer patients at each institution, 16,888 of whom had non-metastatic prostate cancer. A total of 2,397 had been treated with androgen deprivation therapy. The researchers compared these ADT patients with a control group of non-ADT prostate cancer patients, matched according to age and other factors.

Using two different methods of statistical analysis, the team showed that the ADT group, compared to the control group, had significantly more Alzheimer’s diagnoses in the years following the initiation of androgen-lowering therapy. By the most sophisticated measure, members of the ADT group were about 88 percent more likely to get Alzheimer’s.

Source: Penn Medicine