Front Cell Neurosci
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Ginseng is one of the most widely used herbal medicines in the world. It has been used in the treatment of various ailments and to boost immunity for centuries; especially in Asian countries. The most common ginseng variant in traditional herbal medicine is ginseng, which is made from the peeled and dried root of Panax Ginseng. ⋯ It can also prevent neuronal death as a result of stroke, thus decreasing anatomical and functional stroke damage. Although there are diverse studies that have investigated the mechanisms involved in the efficacy of ginseng in treating disorders, there is still much that needs to be clarified. Both in vitro and in vivo studies including randomized controlled clinical trials are necessary to develop in-depth knowledge of ginseng and its practical applications.
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Front Cell Neurosci · Jan 2014
ReviewA molecular web: endoplasmic reticulum stress, inflammation, and oxidative stress.
Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. ⋯ Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction. Dysfunctional UPR pathways have been associated with a wide range of diseases including several neurodegenerative diseases, stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus, cardiovascular disease, and others. In this review, we have discussed the UPR signaling pathways, and networking between ER stress-induced inflammatory pathways, oxidative stress, and mitochondrial signaling events, which further induce or exacerbate ER stress.
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The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. ⋯ We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.
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Front Cell Neurosci · Jan 2014
ReviewThe role of the blood-brain barrier in the development and treatment of migraine and other pain disorders.
The function of the blood-brain barrier (BBB) related to chronic pain has been explored for its classical role in regulating the transcellular and paracellular transport, thus controlling the flow of drugs that act at the central nervous system, such as opioid analgesics (e.g., morphine) and non-steroidal anti-inflammatory drugs. Nonetheless, recent studies have raised the possibility that changes in the BBB permeability might be associated with chronic pain. For instance, changes in the relative amounts of occludin isoforms, resulting in significant increases in the BBB permeability, have been demonstrated after inflammatory hyperalgesia. ⋯ In fact, astrocytes and microglia play a critical role in maintaining the BBB integrity and the activation of those cells is considered a key mechanism underlying chronic pain. Despite the recent advances in the understanding of BBB function in pain development as well as its interference in the efficacy of analgesic drugs, there remain unknowns regarding the molecular mechanisms involved in this process. In this review, we explore the connection between the BBB as well as the blood-spinal cord barrier and blood-nerve barrier, and pain, focusing on cellular and molecular mechanisms of BBB permeabilization induced by inflammatory or neuropathic pain and migraine.
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Front Cell Neurosci · Jan 2014
ReviewGephyrin phosphorylation in the functional organization and plasticity of GABAergic synapses.
Gephyrin is a multifunctional scaffold protein essential for accumulation of inhibitory glycine and GABAA receptors at post-synaptic sites. The molecular events involved in gephyrin-dependent GABAA receptor clustering are still unclear. Evidence has been recently provided that gephyrin phosphorylation plays a key role in these processes. ⋯ Extensively characterized as pivotal enzyme controlling cell proliferation and differentiation, the prolyl-isomerase activity of Pin1 has been shown to regulate protein synthesis necessary to sustain the late phase of long-term potentiation at excitatory synapses, which suggests its involvement at synaptic sites. In this review we summarize the current state of knowledge of the signaling pathways responsible for gephyrin post-translational modifications. We will also outline future lines of research that might contribute to a better understanding of molecular mechanisms by which gephyrin regulates synaptic plasticity at GABAergic synapses.