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Updated time: 28 Oct 2020
Definition: Acetylcholinesterase (AChE) inhibitors are the only drugs that have demonstrated success in slowing shrinkage (atrophy) of the cortex, hippocampus, and basal forebrain, major areas of Alzheimer's disease (AD)-associated brain damage and dementia. The main barrier to taking advantage of this new success in treating, or even preventing, AD is that the old available AChE inhibitors are weakreversible inhibitors that cause intolerable nausea, vomiting, and diarrhea if given in the higher doses needed. A promising new strategy for producing high-level AChE inhibition in the brain as needed for effective treatment of AD is the use of AChE inhibitors that are of a different type, the irreversible inhibitors.
Updated time: 09 Dec 2020
Definition: In the last two decades, non-traditional sports activities characterized by elements such as speed, height, and exposure to natural forces knew a rapid increase in global participation. They are generally referred to as action sports (AS), with the terms adventure sports or extreme sports that could be used as interchangeable synonyms.
Updated time: 05 Nov 2020
Definition: Dysphagia is often unrecognized because many people are unfamiliar with symptoms and signs of dysphagia besides choking during swallowing. Dysphagia screening is therefore important. A good screening should be a quick process and minimally invasive but can determine the likelihood of dysphagia. Here, an algorithm for dysphagia screening is introduced. The algorithm can be used for people unspecialized in dysphagia.
Updated time: 20 Feb 2021
Definition: Many observational and clinical studies have shown that consumption of diets rich in plant polyphenols have beneficial effects on various diseases such as cancer, obesity, diabetes, cardiovascular diseases, and neurodegenerative diseases (NDDs). Animal and cellular studies have indicated that these polyphenolic compounds contribute to such effects. The representative polyphenols are epigallocatechin-3-O-gallate in tea, chlorogenic acids in coffee, resveratrol in wine, and curcumin in curry. The results of human studies have suggested the beneficial effects of consumption of these foods on NDDs, espacially Alzheimer's disease and cellular animal experiments have provided molecular basis to indicate contribution of these representative polyphenols to these effects. This article provides updated information on the effects of these foods and their polyphenols on Alzheimer's disease with discussions on mechanistic aspects of their actions mainly based on the findings derived from basic experiments.
Updated time: 29 Sep 2020
Definition: Astrocyte-neuron crosstalk is a phenomenon in which both of those cell types depend on each other and support their development, genes expression, metabolism, excitability and plasticity. Astrocyte–neuron crosstalk incontrovertibly plays a crucial role in shaping neuronal metabolism. It has been shown that it substantially affects the expression of basal metabolic enzymes in both types of cells, by essentially unknown factor(s) which are released to extracellular space directly and using extracellular vesicles-packed molecules and by cell-to-cell contacts. Additionally, astrocytes support neurons with lactate, which (when secreted during enhanced neuronal activity events) stimulates a formation and maintenece of long-term plastycity phenomena in neurons.
Updated time: 06 Apr 2021
Definition: Astrocytes are cerebral cells present in number close to that on neurons (50-60 mld). For decades they were considered only a glue, offering a mechanical and metaboli
Updated time: 10 Mar 2021
Definition: Autism Spectrum Disorder etiopathogenesis is still unclear, no effective preventive and treatment measures have been identified. Research has focused on the potential role of neuroinflammation and kynurenine pathway. Pre-natal or neonatal infections would induce microglial activation, with secondary consequences on behavior, cognition and neurotransmitter networks. Peripherally higher levels of pro-inflammatory cytokines, and anti-brain antibodies have been identified. Increased frequency of autoimmune diseases, allergies, and recurring infections have been demonstrated both in autistic patients and in their relatives. Genetic studies, also, have identified some important polymorphisms in chromosome loci related to human leukocyte antigen (HLA) system. The persistence of immune-inflammatory deregulation, would lead to mitochondrial dysfunction and oxidative stress, creating a self-sustaining cytotoxic loop.Chronic inflammation actives kynurenine pathway with increase in neurotoxic metabolites and excitotoxicity, causing long-term changes in glutamatergic function, trophic support and synaptic function. Furthermore, overactivation of kynurenines branch, induces depletion of melatonin and serotonin, with ASD symptoms worsening.According to those findings, in subjects genetically predisposed an aberrant neurodevelopment derives by a complex interplay between inflammatory process, mitochondrial dysfunction, oxidative stress, kynurenine pathway overactivation.To validate the previous hypothesis a new translational research approach is necessary.
Updated time: 21 Apr 2021
Definition: Alzheimer’s disease (AD) is characterized by the formation of intracellular aggregate composed of heavily phosphorylated tau protein and extracellular deposit of amyloid-β (Aβ) plaques derived from proteolysis cleavage of amyloid precursor protein (APP). Autophagy refers to the lysosomal-mediated degradation of cytoplasmic constituents, which plays a critical role in maintaining cellular homeostasis. Importantly, recent studies reported that dysregulation of autophagy is associated in the pathogenesis of AD, and therefore, autophagy modulation has gained attention as a promising approach to treat AD pathogenesis. In AD, both the maturation of autolysosomes and its retrograde transports have been obstructed, which causes the accumulation of autophagic vacuoles and eventually leads to degenerating and dystrophic neurites function. However, the mechanism of autophagy modulation in APP processing and its pathogenesis have not yet been fully elucidated in AD. In the early stage of AD, APP processing and Aβ accumulation-mediated autophagy facilitate the removal of toxic protein aggregates via mTOR-dependent and -independent pathways. In addition, a number of autophagy-related genes (Atg) and APP are thought to influence the development of AD, providing a bidirectional link between autophagy and AD pathology.
Entry Collection : Environmental Sciences
Updated time: 16 Apr 2021
Definition: The word autophagy was introduced in late 1963 by the biochemist Christian de Duve  and defines a self-degradative cellular pathway whose intent is to degrade and recycle cellular contents. Autophagy exists in three forms that are classified according to their mechanisms and cellular functions: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). During microautophagy, the cytosolic material is wrapped and transported directly into the lumen of lysosomes. The main function of microautophagy (mA) is to control cell survival and organellar turnover upon nitrogen restriction. CMA has an important role in protein quality control (QC) and is responsible for degrading a specific subset of oxidized and damaged proteins. The selectivity of CMA is conferred by the existence of a specific pentapeptide motif (KFERQ), which is present in the amino acid sequences of all CMA substrates. Undoubtedly, the best-characterized and most prevalent form of autophagy in mammalian cells is macroautophagy (hereafter referred to as autophagy). Autophagy is responsible to capture a wide group of intracellular components, ranging from low-dimensional biological macromolecules to whole organelles, and bring them to the lysosomal compartment. Its physiological value rests on two main activities. On the one hand, autophagy acts as a QC mechanism that reshapes the cell, ensuring the removal of damaged proteins and organelles . Selective forms of autophagy can specifically target mitochondria (mitophagy), the endoplasmic reticulum (ER; reticulophagy), peroxisomes (pexophagy), and lipid droplets (lipophagy).
Updated time: 08 Jan 2021
Definition: Aging and the emergence of age-associated illnesses are one of the major challenges of our present society. Alzheimer’s disease (AD) is closely associated with aging and is defined by increasing memory loss and severe dementia. Currently, there are no therapy options available that halt AD progression.