Neuroscience
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Review
Ubiquitination and E3 Ubiquitin Ligases in Rare Neurological Diseases with Comorbid Epilepsy.
Ubiquitination is a post-translational modification that can dynamically alter the function, degradation and transport of a protein, as well as its interaction with other proteins, and activity of an enzyme. Dysfunctional ubiquitination is detrimental to normal cellular functions, and can result in severe diseases. Over the last decade, although much research has focused on deciphering the role of the ubiquitination/ubiquitin proteasome system (UPS) in the onset and progression of various neurological disorders, the specific relationship between ubiquitination and various epilepsies has not been carefully reviewed. ⋯ Here, we review the role of ubiquitination in maintaining normal cellular activities in neurons and recent findings on the dysregulation of ubiquitination in epilepsy. We particularly focus on rare neurological disorders with comorbid epilepsy in the hope of drawing more attention to this area. Through categorizing epilepsy-associated E3 ubiquitin ligases and their substrates and discussing ubiquitination-related rare neurological disorders, we summarize where the field stands at the moment and what directions we should consider in the future.
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Growing evidence indicates that GABAergic interneurons play a pivotal role to generate brain oscillation patterns, which are fundamental for the mnemonic processing of the hippocampus. While acetylcholine (ACh) is a powerful modulator of synaptic plasticity and brain function, few studies have been focused on the role of cholinergic signaling in the regulation of GABAergic inhibitory synaptic plasticity. ⋯ These forms of iLTP are blocked by the M1 type of mAChR (MR1) or by the group I of mGluR (mGluR1/5) antagonists. These results suggest the existence of spatiotemporal cooperativity between cholinergic and glutamatergic pathways where activation of mAChR serves as a metaplastic switch making glutamatergic synapses capable to induce long-term potentiation at inhibitory synapses, that may contribute to the modulation of brain mechanisms of learning and memory.
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Circular RNAs are an increasingly important topic in non-coding RNA biology, drawing considerable attention in recent years. Accumulating evidence suggests a critical role for circular RNAs in both early and latent stages of disease pathogenesis. ⋯ Disruption of these processes, including those seen in response to brain injury, can have serious consequences such as hemiplegia, aphasia, coma, and death. In this review, we describe the role of circular RNAs in the context of brain injury and explore the potential connection between circular RNAs, brain hypoxic ischemic injury, ischemia-reperfusion injury, and traumatic injury.
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It has long been known that each neuron in both the central and peripheral nervous system has a large number of active zones. Nonetheless, how active zones are regulated to maintain a homeostatic release state and response to the constantly changing environment remains poorly understood. Due to its relatively simple structure and easy accessibility, the neuromuscular synapse (NM-synapse) continues to be used as a model synapse to examine the basic nature of synaptic neurotransmission. ⋯ Furthermore, evoked quantal release has been shown to be highly non-uniform between active zones along nerve terminal branches. How these large numbers of active zones along the same nerve terminal are functionally correlated remains unclear. This review starts with the basic features of quantal neurotransmitter release, then progresses to the current knowledge on how the active zones interact with each other along the same nerve terminal.
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Review
The Interaction Between Contactin and Amyloid Precursor Protein and Its Role in Alzheimer's Disease.
Alzheimer's disease (AD) is a debilitating disease and the most common cause of dementia. As the world population ages even modest advances in therapies and preventative strategies would be of benefit. ⋯ APP is an integral membrane protein which interacts with members of the Contactin family of proteins. Here we review recent progresses in the field and discuss the physiological importance of APP-Contactin interaction, as well as their roles and contributions in the pathophysiology of AD.