Summary
Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked ...to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. Sirtuins (SIRT, silent mating type information regulation 2 homolog in yeast) are NAD‐dependent histone deacetylases involved in aging and longevity. The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD. SIRT3 mRNA and protein levels were significantly decreased in AD cerebral cortex, and Ac‐p53 K320 was significantly increased in AD mitochondria. SIRT3 prevented p53‐induced mitochondrial dysfunction and neuronal damage in a deacetylase activity‐dependent manner. Notably, mitochondrially targeted p53 (mito‐p53) directly reduced mitochondria DNA‐encoded ND2 and ND4 gene expression resulting in increased reactive oxygen species (ROS) and reduced mitochondrial oxygen consumption. ND2 and ND4 gene expressions were significantly decreased in patients with AD. p53‐ChIP analysis verified the presence of p53‐binding elements in the human mitochondrial genome and increased p53 occupancy of mitochondrial DNA in AD. SIRT3 overexpression restored the expression of ND2 and ND4 and improved mitochondrial oxygen consumption by repressing mito‐p53 activity. Our results indicate that SIRT3 dysfunction leads to p53‐mediated mitochondrial and neuronal damage in AD. Therapeutic modulation of SIRT3 activity may ameliorate mitochondrial pathology and neurodegeneration in AD.
Although many reports have revealed the importance of defective microglia-mediated amyloid β phagocytosis in Alzheimer's disease (AD), the underlying mechanism remains to be explored. Here we ...demonstrate that neurons in the brains of patients with AD and AD mice show reduction of sphingosine kinase1 (SphK1), leading to defective microglial phagocytosis and dysfunction of inflammation resolution due to decreased secretion of specialized proresolving mediators (SPMs). Elevation of SphK1 increased SPMs secretion, especially 15-R-Lipoxin A4, by promoting acetylation of serine residue 565 (S565) of cyclooxygenase2 (COX2) using acetyl-CoA, resulting in improvement of AD-like pathology in APP/PS1 mice. In contrast, conditional SphK1 deficiency in neurons reduced SPMs secretion and abnormal phagocytosis similar to AD. Together, these results uncover a novel mechanism of SphK1 pathogenesis in AD, in which impaired SPMs secretion leads to defective microglial phagocytosis, and suggests that SphK1 in neurons has acetyl-CoA-dependent cytoplasmic acetyltransferase activity towards COX2.
Ginseng in Traditional Herbal Prescriptions Park, Ho Jae; Kim, Dong Hyun; Park, Se Jin ...
Journal of Ginseng Research/Journal of ginseng research,
07/2012, Volume:
36, Issue:
3
Journal Article
Peer reviewed
Open access
Panax ginseng Meyer has been widely used as a tonic in traditional Korean, Chinese, and Japanese herbal medicines and in Western herbal preparations for thousands of years. In the past, ginseng was ...very rare and was considered to have mysterious powers. Today, the efficacy of drugs must be tested through well-designed clinical trials or meta-analyses, and ginseng is no exception. In the present review, we discuss the functions of ginseng described in historical documents and describe how these functions are taken into account in herbal prescriptions. We also discuss the findings of experimental pharmacological research on the functions of ginseng in ginseng-containing prescriptions and how these prescriptions have been applied in modern therapeutic interventions. The present review on the functions of ginseng in traditional prescriptions helps to demystify ginseng and, as a result, may contribute to expanding the use of ginseng or ginseng-containing prescriptions.
The degradation of thermal properties due to ageing such as burning rate and exothermic heat release are unsolved issues faced during a long-term storage of the pyrotechnic substances. Accordingly, ...we employed various non-calorimetric methods to investigate the thermal performance of pyrotechnic delay, which is exposed to various moisture-rich conditions at extended durations. The chemical and physical changes in the compositions of a pyrotechnic delay comprised of metal fuel (Zr-Ni alloy) and oxidants (KClO
, BaCrO
) are analysed for four different relative humidity levels using X-ray photoelectron spectroscopy, X-ray diffraction, scanning electron microscope and laser-induced breakdown spectroscopy. The calculations using the NASA Chemical Equilibrium with Applications (CEA) software indicated that the heat of reaction for the components stored under the moisture-rich conditions is reduced by more than 50%. Unlike the conventional calorimetric analysis, the present non-calorimetric approach provided the compositional changes as well as the cause and effect of the relevant ageing process of pyrotechnic delay.
Single-crystal, conventional, and refined polycrystalline (LiNi0.9Co0.05Mn0.05O2) cathodes were prepared, and their performances and capacity fading behaviors in half cells were compared. The rate ...capability and cycling stability of polycrystalline cathodes are better than those of single-crystal cathodes. Furthermore, the performance of the refined polycrystalline cathode is markedly improved owing to the elongated, radially oriented primary particles of the cathode, which effectively suppresses severe intergranular microcracking during cycling. The rapid capacity fading behavior of single-crystal cathode stems from kinetically hindered Li+ intercalation, resulting from its long Li+ diffusion paths and microstructural damage caused by repeated cycling. The accumulation of internal stress in large single-crystal particles during cycling leads to fracturing and the development of an extensive network of regularly spaced slip bands. Structural damage concentrated in these slip bands causes inhomogeneities in the distribution of Li+ within particles and hinders Li+ diffusion, leading to poor electrochemical performance.
A novel micro-structured PDMS coating with high durability and relatively low friction was successfully replicated from a lotus leaf. Unlike the bio-inspired coatings developed previously, the ...micro-structured PDMS specimen could be fabricated in the form of a coating which could be successfully deposited on a solid surface. Results showed that friction and wear of the micro-structured PDMS specimens were significantly lower than those of the smooth specimens. It was also found that the wear resistance of micro-structured PDMS coating with 200μm thickness was much higher than that of the micro-structured PDMS bulk specimen. The drastically high durability of the PDMS coating specimen was attributed to frictional energy dissipation through elastic deformation of the micro-structures.
LiNi1–x–y–z Co x Mn y Al z O2 (NCMA) cathodes have attracted public attention owing to their improved durability by leveraging the advantages of NCM and NCA cathodes. As the Ni content approaches ...90%, however, it is challenging to realize high-energy Ni-rich NCMA cathodes without sacrificing durability. Herein, we improve the cycling stability of a Ni-rich LiNi0.93Co0.03Mn0.03Al0.01O2 (NCMA93) cathode using a combination strategy involving microstructural refinement and surface modification. The F-coating-induced protective layer of the F-coated, Sb-doped NCMA93 cathode combined with its engineered microstructure enables the formation of a robust cathode–electrolyte interphase (CEI) layer on the cathode surface, which suppresses surface degradation to afford a long battery life. However, the F coating alone does not significantly improve the cycling stability of cathode because it suffers severe microcracking during cycling owing to its suboptimal microstructure. To realize a cathode with a long lifespan, a robust CEI layer should be generated and maintained on the cathode without severe microcracking.
This study was aimed at enhancing surface plasmon resonance through a combination of Ag nanoparticles (NPs) and an asymmetric crater structure capable of concentrating light. The crater structure was ...fabricated via wet-chemical etching of a GaAs(100) wafer, after which an Ag film was deposited inside, and subjected to rapid thermal annealing to form NPs. The results were analysed in terms of the magnitude of the Raman intensity, from which an optimal combination of annealing temperature and film thickness was determined. Ag nanowires (NWs) were also spray-coated onto the AgNPs to elucidate the effect of coupling the NPs with the NWs. The Raman intensity was 22 times higher inside the crater with AgNPs and NWs than on a flat area without NPs; however, further increases in the amount of AgNWs resulted in greater coverage of the AgNPs, which reduced the Raman intensity. We expect the proposed method for Raman signal enhancement to promote further development and applications of surface-enhanced Raman scattering (SERS) spectroscopy.
Objective:
Alzheimer disease (AD) brains are deficient in brain‐derived neurotrophic factor (BDNF), which regulates synaptic plasticity and memory. MicroRNAs (miRNAs) are ∼22‐nucleotide small ...noncoding RNAs that control a variety of physiological and disease processes. Here, we show that miR‐206 regulates BDNF and memory function in AD mice.
Methods:
Expression of miRNAs was analyzed in Tg2576 AD transgenic mice and human AD brain samples. Regulation of BDNF by a selected miRNA was validated by in silico prediction, target gene luciferase assay, and dendritic spine responses in neurons. AM206, a neutralizing inhibitor of miR‐206 (antagomir), was injected into the third ventricle of Tg2576 mice, after which memory function, synaptogenesis, neurogenesis, and target gene expression were assessed. For noninvasive delivery, antagomirs were administered intranasally.
Results:
The brains of Tg2576 mice and the temporal cortex of human AD brains had increased levels of miR‐206. This miRNA targeted BDNF transcripts, and AM206 prevented the detrimental effects of amyloid‐β42 on BDNF and dendritic spine degeneration in Tg2576 neurons. Injection of AM206 into the cerebral ventricles of AD mice increased the brain levels of BDNF and improved their memory function. In parallel, AM206 enhanced the hippocampal synaptic density and neurogenesis. Furthermore, intranasally administered AM206 also reached the brain and increased BDNF levels and memory function in AD mice.
Interpretation:
Our findings demonstrate a novel miRNA‐dependent regulation of BDNF in AD and suggest possible therapeutic approaches, such as noninvasive intranasal delivery of AM206. ANN NEUROL 2012;72:269–277.
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