Unraveling Alzheimer’s: New Study Documents How Brain Cells Go Bad
In a first-of-its-kind study, UNC researchers show how a damaging cascade of events inside brain cells – and related to Alzheimer’s disease – can be stopped or reversed.
In a first-of-its-kind study, UNC researchers show how a damaging cascade of events inside brain cells – and related to Alzheimer’s disease – can be stopped or reversed.
The axon guidance cue netrin-1 and its receptor DCC promote axon branching in developing cortical neurons. In this study, we detail a novel molecular mechanism by which the brain-enriched E3 ubiquitin ligase TRIM9 orchestrates multimerization of DCC, requisite activation of FAK and Src family kinases, and increases in exocytic vesicle fusion, all during netrin-dependent neuronal morphogenesis. We are the first to show that non-degradative ubiquitination of a receptor alters kinase activation and signaling pathways during morphogenesis.
The focus of this grant is to illuminate a novel mechanism for dendritic spine pruning in the mammalian neocortex by immunoglobulin (Ig)-class cell adhesion molecules and secreted Semaphorins. The overall goal is to identify mechanisms that govern synaptic connectivity in the mammalian neocortex, and to elucidate how their deficiency contributes to abnormal brain wiring relevant to neurodevelopmental disorders.
Microcephaly is a hallmark of Angelman syndrome (AS), a debilitating neurodevelopmental disorder that results from loss of function of the HECT domain E3 ubiquitin ligase, UBE3A. However, until recently, the underlying causes of slowed brain growth in individuals with AS had gone unstudied, resulting in significant gaps in understanding of the pathogenesis of the disorder.
An antenna-like structure on cells, once considered a useless vestige, appears to be important for proper brain development in mammals and when impaired can cause defects in the brain’s wiring similar to what’s seen in autism, schizophrenia, and other neuropsychiatric disorders. In lab experiments, UNC School of Medicine scientists prevented these wiring defects by restoring signaling though these antenna-like structures called primary cilia.
The study was published on August 7, 2017 in Developmental Cell.
The Cohen Lab and NC State researchers team up to reverse TDP-43 protein aggregation, a hallmark of degenerative diseases.
In the study published July 6th in the journal Neuron titled, “Network-level Control of Frequency Tuning in Auditory Complex”, Kato et al. found a neuronal network basis for how our brain precisely represents the external world.
Anne Marion Taylor’s lab receives an American Heart Association grant to further their research investigating how axon damage causes synaptic remodeling following stroke
“In a new study, Emerson et al. show that brain function in infancy can be used to accurately predict which high-risk infants will later receive an autism diagnosis…These findings must be replicated, but they represent an important step toward the early identification of individuals with autism before its characteristic symptoms develop.” (http://stm.sciencemag.org/content/9/393/eaag2882)
In the journal Cancer Research, UNC Lineberger researchers led by Neuroscience Center member Timothy R. Gershon, MD, PhD, report in the latest in a series of attempts to shut down the energy production machinery in medulloblastoma, the most common malignant brain tumor in children. The findings may help researchers identify a suitable therapeutic target within the sugar metabolism pathway, and provide clues to a scientific mystery surrounding the confounding way that some cancer cells get energy from sugar.