Stanford University School of Medicine researchers have identified several small molecules that mimic a key but cumbersome protein in the brain, a discovery that could open the door to new therapies for a variety of brain disorders. The protein, designated by the acronym BDNF, is known to be involved in important brain functions that include memory and learning. "These small molecules could be the basis of drugs that provide entirely new avenues of treatment for a large number of neuropsychiatric disorders such as Alzheimer's, Huntington's and depression, " said Frank Longo, MD, PhD, professor and chair of neurology and neurological sciences and senior author of a study to be published online April 19 in the Journal of Clinical Investigation. BDNF belongs to a family of proteins called nerve growth factors, which are critical during development of the nervous system.
Ku70, a component of the DNA repair complex, is shown to be a new critical player in the DNA damage-linked pathologies of Huntington's disease (HD), according to a study in the May 3 issue of the Journal of Cell Biology. DNA repair defends against naturally occurring or disease-related DNA damage during the long lifespan of neurons. Impairments to this process underlie "polyQ" diseases, a major group of hereditary neurodegenerative disorders that includes HD. Understanding the multiple pathogenic pathways that lead to such DNA repair dysfunction is key for the development of new therapies. In this study, Hitoshi Okazawa and colleagues report that expression of mutant huntingtin (Htt) - the protein responsible for HD - in neurons causes double-strand breaks (DSBs) in genomic DNA and impairs DNA repair.
Eventual Huntington's Drug May Have Clear Path To Affected Brain Region, Solomon Snyder Tells Pharmacy Students
If a drug was developed to block a key protein linked to the onset of Huntington's Disease, it could have a clear path to the part of the brain most affected by the disease, while not bothering other parts of the brain and body, said distinguished neuroscientist Solomon H. Snyder, MD, to an audience of about 300 students and faculty at the University of Maryland, Baltimore (UMB). Snyder said, "Even though there is a market out there of only 100, 000 patients, " his laboratory at Johns Hopkins University is currently partnering with big pharmaceutical companies to develop such a drug, one to block binding of the Rhes protein to mutant huntingtin protein, a genetically altered protein in Huntington's Disease which kills cells in the brain's corpus striatum. Snyder presented the annual Ellis S.
They might not be known for their big brains, but fruit flies are helping to make scientists and doctors smarter about what causes Huntington's disease and how to treat it. New research, published in the journal GENETICS describes a laboratory test that allows scientists to evaluate large numbers of fruit fly genes for a possible role in the formation of plaque-like protein aggregates within cells. Those genes often have counterparts in humans, which might then be manipulated to stop or slow the formation of plaque-like protein aggregates, the hallmark of Huntington's and several other neurodegenerative diseases. "Aggregate formations are closely linked to aging and brain diseases, " said Sheng Zhang, Ph.D, a researcher involved in the work from the Research Center for Neurodegenerative Diseases, the Brown Foundation Institute of Molecular Medicine, the University of Texas Health Science Center at Houston.
Program Will Use Stem Cell Modeling And Genome Sequencing To Identify And Screen Potential Therapies For Huntington's Disease
The Institute for Systems Biology (ISB) of Seattle, WA, is collaborating with the Gladstone Institute of Neurological Disease (GIND) and its Taube-Koret Center for Huntington's Disease Research to use whole-genome sequencing to identify genes and novel drug targets related to the onset and progression of Huntington's disease (HD). The research team, led by GIND associate director and senior investigator Steven Finkbeiner, MD, PhD, will also use induced pluripotent stem (iPS) cells from patients with HD to screen for drugs that might delay, prevent, or even reverse this devastating condition. HD is an inherited degenerative brain disorder attributed to a single gene mutation. However, Finkbeiner, who directs the Taube-Koret Center for Huntington's Disease Research, explained that other genes may regulate the onset and progression of the disease and influence the particular symptoms that each individual experience.