A new study of the brain's master circadian clock - known as the suprachiasmatic nucleus, or SCN - reveals that a key pattern of rhythmic neural activity begins to decline by middle age. The study, whose senior author is UCLA Chancellor Gene Block, may have implications for the large number of older people who have difficulty sleeping and adjusting to time changes. "Aging has a profound effect on circadian timing, " said Block, a professor of psychiatry and biobehavioral sciences and of physiological science. "It is very clear that animals' circadian systems begin to deteriorate as they age, and humans have enormous problems with the quality of their sleep as they age, difficulty adjusting to time-zone changes and difficulty performing shift-work, as well as less alertness when awake.
A new study describes how hyperactivation of AMP-activated protein kinase (AMPK) promotes neurodegeneration in Huntington's disease (HD). The article appears online on July 18, 2011, in The Journal of Cell Biology. The aggregation of mutant Huntingtin protein in HD disrupts many cellular processes, including metabolism. AMPK - a protein that balances a cell's energy production and usage - is abnormally active in the brains of mice with HD, but whether the kinase protects neurons from the metabolic imbalances associated with HD or whether AMPK contributes to neuronal death is unknown. Yijuang Chern and colleagues determined that the alpha1 isoform of AMPK was specifically activated and translocated into the nuclei of neurons in a mouse model of HD, whereas AMPK-alpha2 was unaffected. An inhibitor of Ca2+/calmodulin-dependent protein kinase II reduced AMPK activity, suggesting that AMPK-alpha1 is activated by this kinase, probably because Ca2+ signaling is disrupted in HD neurons.
UT Southwestern Medical Center researchers have identified compounds that appear to inhibit a signaling pathway in Huntington's disease, a finding that may eventually lead to a potential drug therapy to help slow the progression of degenerative nerve disorders. "Our studies have uncovered a new therapeutic target for Huntington's disease treatment and possibly for other neurodegenerative diseases, " said Dr. Ilya Bezprozvanny, professor of physiology and senior author of the study, published in today's issue of Chemistry and Biology. "In addition, we now have this new series of compounds that gives us a tool to study the pathogenesis of Huntington's disease." Huntington's disease is a fatal genetic disorder in which certain brain cells waste away. More than 250, 000 people in the U.S.
A Key Trigger To A Rare But Deadly Neurodegenerative Disease Revealed By Molecular Biophysics Professor
Jeremy Smith, Governor's Chair for Molecular Biophysics at the University of Tennessee, Knoxville, has helped reveal a key trigger of Gerstmann-StrĂ ussler-Scheinker (GSS) syndrome, a rare but deadly neurodegenerative disease. The finding could have far-reaching implications for the treatment of other neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's. Smith conducted his research with two collaborators in Italy: Isabella Daidone, a former postdoctoral researcher of his who is now at the University of L'Aquila, and Alfredo Di Nola of the University of Rome "La Sapienza." Most GSS patients begin developing symptoms in their late fifties. Symptoms include loss of memory, difficulty speaking, and unsteadiness and lead to progressive dementia, and then death within a few months or years.
Johns Hopkins researchers have identified a natural mechanism that might one day be used to block the expression of the mutated gene known to cause Huntington's disease. Their experiments offer not an immediate cure, but a potential new approach to stopping or even preventing the development of this relentless neurodegenerative disorder. Huntington's disease is a rare, fatal disorder caused by a mutation in a single gene and marked by progressive brain damage. Symptoms, which typically first appear in midlife, include jerky twitch-like movements, coordination troubles, psychiatric disorders and dementia. Although the gene responsible for Huntington's was identified in 1993, there is no cure, and there are no treatments are available even to slow its progression. The disorder is caused by a mutation in the huntingtin gene (HTT).