Si allegano i bandi per le borse di studio per i posti di biologa e psicologo.
Two studies from the Peter O’Donnell Jr. Brain Institute demonstrate in animals how a vaccine containing DNA of the toxic beta-amyloid protein elicits a different immune response that may be safe for humans.
The vaccine, which will likely be tested further by the U.S. Food and Drug Administration, is on a shortlist of promising antibody treatments that may eventually help settle a high-stakes debate of whether amyloid is a vital target for preventing or curing Alzheimer’s.
“If you look at the hard reality, the odds are against us because so many therapies have failed through the years. But this has potential,” said Dr. Roger Rosenberg, co-author of the studies and Director of the Alzheimer’s Disease Center at UT Southwestern Medical Center.
Dr. Rosenberg notes that earlier research established that antibodies significantly reduce amyloid buildup in the brain, but he needed to find a safe way to introduce these into the body. A vaccine developed elsewhere showed promise in the early 2000s, but when tested in humans it caused brain swelling in some patients.
Dr. Rosenberg’s idea was to start with DNA coding for amyloid and inject it into the skin rather than the muscle. The injected skin cells make the amyloid protein, and the body responds by producing new antibodies that inhibit the buildup of amyloid, which some scientists blame for destroying neurons.
New biomarkers identified by a research team in the Perelman School of Medicine at the University of Pennsylvania could help predict which Parkinson’s disease patients will suffer significant cognitive deficits within the first three years of their diagnosis. The results of the analysis from the international Parkinson’s Progression Markers Initiative (PPMI) are published this week in the open-access journal PLoS ONE.
“The results of this study improve our understanding of the changes in brain function that occur with initial cognitive changes in early Parkinson’s disease,” said Daniel Weintraub, MD, a professor of Psychiatry and lead author. “This could eventually lead to improved clinical care and development of therapies to treat this symptom.”
Dr. Weintraub led the team that analyzed data and samples from 423 newly diagnosed and untreated Parkinson’s disease patients who showed no signs of dementia at the time of their enrollment in PPMI, a landmark observational study launched in 2010 and sponsored by The Michael J. Fox Foundation for Parkinson’s Research.
Three years after enrollment, between 15 and 38 percent of these participants had developed cognitive impairment. The authors assessed brain scans, genetic tests and analyses of cerebrospinal fluid (CSF) and found cognitive decline correlated with several biomarkers: changes in the dopamine system, global brain atrophy, particular genetic mutations, and markers of Alzheimer’s disease.
Resveratrol protects neuronal-like cells expressing mutant Huntingtin from dopamine toxicity by rescuing ATG4-mediated autophagosome formation
Parkinsonian-like motor deficits in Huntington's Disease (HD) patients are associated with abnormal dopamine neurotransmission in the striatum. Dopamine metabolism leads to the formation of oxidized dopamine quinones that exacerbates mitochondrial dysfunction with production of reactive oxygen species (ROS) that eventually lead to neuronal cell death. We have previously shown that dopamine-induced oxidative stress triggers apoptotic cell death in dopaminergic neuroblastoma SH-SY5Y cells hyper-expressing the mutant polyQ Huntingtin (polyQ-Htt) protein. Dopamine toxicity was paralleled by impaired autophagy clearance of the polyQ-Htt aggregates. In this study, we found that Dopamine affects the stability and function of ATG4, a redox-sensitive cysteine-protein involved in the processing of LC3, a key step in the formation of autophagosomes. Resveratrol, a dietary polyphenol with anti-oxidant and pro-autophagic properties, has shown neuroprotective potential in HD. Yet the molecular mechanism through which Resveratrol can protect HD cells against DA is not known. Here, we show that Resveratrol prevents the generation of ROS, restores the level of ATG4, allows the lipidation of LC3, facilitates the degradation of polyQ-Htt aggregates and protects the cells from Dopamine toxicity.
The present findings provide a mechanistic explanation of the neuroprotective activity of Resveratrol and support its inclusion in a therapeutic regimen to slow down HD progression.