The genetic basis of hydrocephalus: genes, pathways, mechanisms, and global impact.

Hydrocephalus (HC) is a heterogenous disease characterized by alterations in cerebrospinal fluid (CSF) dynamics that may cause increased intracranial pressure. HC is a component of a wide array of genetic syndromes as well as a secondary consequence of brain injury (intraventricular hemorrhage (IVH), infection, etc.) that can present across the age spectrum, highlighting the phenotypic heterogeneity of the disease.

Immunotherapy for Pediatric Brain and Spine Tumors: Current State and Future Directions.

Background: Brain tumors are the most common solid tumors and the leading cause of cancer-related deaths in children. Incidence in the USA has been on the rise for the last 2 decades. While therapeutic advances in diagnosis and treatment have improved survival and quality of life in many children, prognosis remains poor and current treatments have significant long-term sequelae.

Males and females differ in the regulation and engagement of, but not requirement for, protein degradation in the amygdala during fear memory formation.

Over the last decade, strong evidence has emerged that protein degradation mediated by the ubiquitin-proteasome system is critical for fear memory formation in the amygdala. However, this work has been done primarily in males, leaving unanswered questions about whether females also require protein degradation during fear memory formation. Here, we found that male and female rats differed in their engagement and regulation of, but not need for, protein degradation in the amygdala during fear memory formation.

Males and Females Differ in the Subcellular and Brain Region Dependent Regulation of Proteasome Activity by CaMKII and Protein Kinase A.

The ubiquitin-proteasome system (UPS) controls the degradation of ~90% of short-lived proteins in cells and is involved in activity- and learning-dependent synaptic plasticity in the brain. Calcium/calmodulin dependent protein kinase II (CaMKII) and Protein Kinase A (PKA) can regulate activity of the proteasome. However, there have been a number of conflicting reports regarding under what conditions CaMKII and PKA regulate proteasome activity in the brain.

Quantifying Subcellular Ubiquitin-proteasome Activity in the Rodent Brain.

The ubiquitin-proteasome system is a key regulator of protein degradation and a variety of other cellular processes in eukaryotes. In the brain, increases in ubiquitin-proteasome activity are critical for synaptic plasticity and memory formation and aberrant changes in this system are associated with a variety of neurological, neurodegenerative and psychiatric disorders. One of the issues in studying ubiquitin-proteasome functioning in the brain is that it is present in all cellular compartments, in which the protein targets, functional role and mechanisms of regulation can vary widely.

Distinct subcellular changes in proteasome activity and linkage-specific protein polyubiquitination in the amygdala during the consolidation and reconsolidation of a fear memory.

Numerous studies have supported a critical role for the ubiquitin-proteasome system (UPS) in the memory consolidation and reconsolidation processes. The protein targets and functional role of ubiquitin-proteasome activity can vary widely across cellular compartments, however, it is unknown how UPS activity changes within the nuclear, cytoplasmic, and synaptic regions in response to learning or memory retrieval. Additionally, while previous studies have focused on degradation-specific protein polyubiquitination, it is unknown how learning alters other polyubiquitin tags that are not targeted by the proteasome.

The Ubiquitin-Proteasome System and Memory: Moving Beyond Protein Degradation.

Cellular models of memory formation have focused on the need for protein synthesis. Recently, evidence has emerged that protein degradation mediated by the ubiquitin-proteasome system (UPS) is also important for this process. This has led to revised cellular models of memory formation that focus on a balance between protein degradation and synthesis.