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131.
《Autophagy》2013,9(11):1686-1687
The most common neurodegenerative diseases are characterized by the accumulation of misfolded proteins. Tauopathies, which include Alzheimer disease, progressive supranuclear palsy, corticobasal degeneration, Pick disease and cases of frontotemporal dementia and parkinsonism linked to chromosome 17, are characterized by the accumulation of hyperphosphorylated and filamentous MAPT/tau protein. The pathological mechanisms involved in MAPT protein accumulation are not well understood, but a possible impairment of protein degradation pathways has been suggested. We investigated the effects of autophagy stimulation on MAPT pathology in a model tauopathy, the human mutant P301S MAPT transgenic mouse line. In the brain of the trehalose-treated mutant mice, autophagy is activated and a reduced number of neurons containing MAPT inclusions, as well as a decreased amount of insoluble MAPT, are observed. The improvement of MAPT pathology is associated with increased nerve cell survival. Moreover, MAPT inclusions colocalize with SQSTM1/p62- and LC3-positive puncta, suggesting the colocalization of MAPT aggregates with autophagic vacuoles. Autophagy is not activated in the spinal cord of the human P301S MAPT transgenic mice and neuronal survival, as well as MAPT pathology, is unaffected. This study supports a role for autophagy stimulation in the degradation of MAPT aggregates and opens new perspectives for the investigation of autophagy as a pathological mechanism involved in neurodegenerative diseases. 相似文献
132.
Ryann M. Fame Christian Cortés-Campos Hazel L. Sive 《BioEssays : news and reviews in molecular, cellular and developmental biology》2020,42(3):1900186
The brain ventricular system is a series of connected cavities, filled with cerebrospinal fluid (CSF), that forms within the vertebrate central nervous system (CNS). The hollow neural tube is a hallmark of the chordate CNS, and a closed neural tube is essential for normal development. Development and function of the ventricular system is examined, emphasizing three interdigitating components that form a functional system: ventricle walls, CSF fluid properties, and activity of CSF constituent factors. The cellular lining of the ventricle both can produce and is responsive to CSF. Fluid properties and conserved CSF components contribute to normal CNS development. Anomalies of the CSF/ventricular system serve as diagnostics and may cause CNS disorders, further highlighting their importance. This review focuses on the evolution and development of the brain ventricular system, associated function, and connected pathologies. It is geared as an introduction for scholars with little background in the field. 相似文献
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Notch signaling is an evolutionarily conserved signaling pathway and is essential for cell-fate specification in metazoans. Dysregulation of Notch signaling results in various human diseases, including cardiovascular defects and cancer. In 2000, Fringe, a known regulator of Notch signaling, was discovered as a Notch-modifying glycosyltransferase. Since then, glycosylation—a post-translational modification involving literal sugars—on the Notch extracellular domain has been noted as a critical mechanism for the regulation of Notch signaling. Additionally, the presence of diverse O-glycans decorating Notch receptors has been revealed in the extracellular domain epidermal growth factor-like (EGF) repeats. Here, we concisely summarize the recent studies in the human diseases associated with aberrant Notch glycosylation. 相似文献
136.
Bor Luen Tang 《Journal of cellular physiology》2020,235(11):7653-7662
Prolonged survival of a typical postmitotic neuron hinges on a balance between multiple processes, among these are a sustenance of ATP production and protection against reactive oxygen species. In neuropathological conditions, mitochondrial defects often lead to both a drop in ATP levels, as well as increase reactive oxygen species production from inefficient electron transport processes and NADPH-oxidases activities. The former often resulted in the phenomenon of compensatory aerobic glycolysis. The latter stretches the capacity of the cell's redox buffering capacity, and may lead to damages of key enzymes involved in energy metabolism. Several recent reports have indicated that enhancing glucose availability and uptake, as well as increasing glycolytic flux via pharmacological or genetic manipulation of glycolytic enzymes, could be protective in animal models of several major neurodegenerative diseases, including Parkinson's disease, Huntington's disease, and Amyotrophic lateral sclerosis. Activation of canonical Wnt signaling, which improves disease symptoms in mouse models of Alzheimer's disease also appears to work via an elevation of glycolytic enzymes and enhance glucose metabolism. Here, I discuss these findings and the possible underlying mechanisms of how an increase in glucose uptake and glycolysis could be neuroprotective. Increased glycolytic production of ATP would help alleviate energy deficiency, and ATP's hydrotropic effect may enhance solubility and clearance of toxic aggregates prevalent in many neurodegenerative diseases. Furthermore, channeling of glucose into the Pentose Phosphate Pathway would increase the redox buffering capacity of the cell. 相似文献
137.
Qiong Li Fan Liu Rui Dang Chunyue Feng Rui Xiao Ye Hua Wei Wang Zhi Jia Dayong Liu 《Journal of cellular physiology》2020,235(12):9691-9701
We wished to evaluate whether epigenetic modifiers have a beneficial effect on treating experimental periodontitis and mechanisms for regulating the cell fate of mesenchymal stem cells (MSCs) in inflammatory microenvironments. We isolated MSCs from healthy and inflamed gingival tissues to investigate whether trichostatin A (TSA) could improve osteogenic differentiation and resolve inflammation in vitro. The tissue regenerative potentials were evaluated when treated with a temperature-dependent, chitosan-scaffold-encapsulated TSA, in a rat model of periodontitis. After induction with the conditioned medium, TSA treatment increased the osteogenic differentiation potential of inflamed MSCs and healthy MSCs. In addition, interleukin-6 and interleukin-8 levels in supernatants were significantly decreased after TSA treatment. Moreover, TSA promoted osteogenic differentiation by inhibiting nuclear factor-κB (p65) DNA binding in MSCs. In rats with experimental periodontitis, 7 weeks after local injections of chitosan-scaffold-encapsulated TSA, histology and microcomputed tomography showed a significant increase in alveolar bone volume and less inflammatory infiltration compared with vehicle-treated rats. The concentrations of interferon-γ and interleukin-6 were significantly decreased in the gingival crevicular fluid after TSA treatment. This study demonstrated that TSA had anti-inflammatory properties and could promote periodontal tissue repair, which indicated that epigenetic modifiers hold promise as a potential therapeutic option for periodontal tissue repair. 相似文献
138.
Mahdi Arzanlou Abolfazl Narmani Somayeh Moshari Sima Khodaei Asadollah Babai-Ahari 《Archives Of Phytopathology And Plant Protection》2013,46(10):1168-1181
In recent years, grapevine trunk diseases have gained growing attentions due to worldwide incidence of the disease. In a survey on fungal agents associated with grapevine trunk diseases in northern Iran, wood samples were collected from grapevines having the symptoms of declination. Isolation was made using routine plant pathology methods. A coelomycetous fungus with appendage-bearing conidia was recovered from symptomatic tissues. Based on morphological and cultural characteristics, the causal agent of the disease was identified as Truncatella angustata. The identity of the species was further confirmed by sequence data of internal transcribed spacer-rDNA region. A phylogeny inferred using sequence data obtained in this study, together with the sequences from GenBank, clustered our isolates together with T. angustata known from other host plant species. Pathogenicity tests performed on detached shoots of grapevines led to the same symptoms as observed in field conditions. This is first study on the pathogenicity of T. angustata on grapevine in Iran and first report on the occurrence of T. angustata on grapevine in Iran. 相似文献
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Victoria V. Nefedova Petr N. Datskevich Maria V. Sudnitsyna Sergei V. Strelkov Nikolai B. Gusev 《Biochimie》2013
Some physico-chemical properties of R140G and K141Q mutants of human small heat shock protein HspB1 associated with hereditary peripheral neuropathy were analyzed. Mutation K141Q did not affect intrinsic Trp fluorescence and interaction with hydrophobic probe bis-ANS, whereas mutation R140G decreased both intrinsic fluorescence and fluorescence of bis-ANS bound to HspB1. Both mutations decreased thermal stability of HspB1. Mutation R140G increased, whereas mutation K141Q decreased the rate of trypsinolysis of the central part (residues 5–188) of HspB1. Both the wild type HspB1 and its K141Q mutant formed large oligomers with apparent molecular weight ∼560 kDa. The R140G mutant formed two types of oligomers, i.e. large oligomers tending to aggregate and small oligomers with apparent molecular weight ∼70 kDa. The wild type HspB1 formed mixed homooligomers with R140G mutant with apparent molecular weight ∼610 kDa. The R140G mutant was unable to form high molecular weight heterooligomers with HspB6, whereas the K141Q mutant formed two types of heterooligomers with HspB6. In vitro measured chaperone-like activity of the wild type HspB1 was comparable with that of K141Q mutant and was much higher than that of R140G mutant. Mutations of homologous hot-spot Arg (R140G of HspB1 and R120G of αB-crystallin) induced similar changes in the properties of two small heat shock proteins, whereas mutations of two neighboring residues (R140 and K141) induced different changes in the properties of HspB1. 相似文献