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Seyed Fazel Nabavi Antoni Sureda Ahmad Reza Dehpour Samira Shirooie Ana Sanches Silva Kasi Pandima Devi Touqeer Ahmed Nafeesa Ishaq Rabia Hashim Eduardo Sobarzo-Sánchez Maria Daglia Nady Braidy Mariateresa Volpicella Rosa Anna Vacca Seyed Mohammad Nabavi 《Biotechnology advances》2018,36(6):1768-1778
In the present paper, we will discuss on the importance of autophagy in the central nervous system, and outline the relation between autophagic pathways and the pathogenesis of neurodegenerative disorders. The potential therapeutic benefits of naturally occurring phytochemicals as pharmacological modulators of autophagy will also be addressed. Our findings provide renewed insight on the molecular modes of protection by polyphenols, which is likely to be at least in part mediated not only by their potent antioxidant and anti-inflammatory effects, but also through modulation of autophagic processes to remove the aberrant protein aggregates. 相似文献
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Hye-Rim Shin Rabia Islam Won-Joon Yoon Taegyung Lee Young-Dan Cho Han-sol Bae Bong-Su Kim Kyung-Mi Woo Jeong-Hwa Baek Hyun-Mo Ryoo 《The Journal of biological chemistry》2016,291(11):5555-5565
The canonical Wnt signaling pathway, in which β-catenin nuclear localization is a crucial step, plays an important role in osteoblast differentiation. Pin1, a prolyl isomerase, is also known as a key enzyme in osteogenesis. However, the role of Pin1 in canonical Wnt signal-induced osteoblast differentiation is poorly understood. We found that Pin1 deficiency caused osteopenia and reduction of β-catenin in bone lining cells. Similarly, Pin1 knockdown or treatment with Pin1 inhibitors strongly decreased the nuclear β-catenin level, TOP flash activity, and expression of bone marker genes induced by canonical Wnt activation and vice versa in Pin1 overexpression. Pin1 interacts directly with and isomerizes β-catenin in the nucleus. The isomerized β-catenin could not bind to nuclear adenomatous polyposis coli, which drives β-catenin out of the nucleus for proteasomal degradation, which consequently increases the retention of β-catenin in the nucleus and might explain the decrease of β-catenin ubiquitination. These results indicate that Pin1 could be a critical target to modulate β-catenin-mediated osteogenesis. 相似文献
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Revisiting Kadenbach: Electron flux rate through cytochrome c‐oxidase determines the ATP‐inhibitory effect and subsequent production of ROS 下载免费PDF全文
Sebastian Vogt Annika Rhiel Petra Weber Rabia Ramzan 《BioEssays : news and reviews in molecular, cellular and developmental biology》2016,38(6):556-567
Mitochondrial respiration is the predominant source of ATP. Excessive rates of electron transport cause a higher production of harmful reactive oxygen species (ROS). There are two regulatory mechanisms known. The first, according to Mitchel, is dependent on the mitochondrial membrane potential that drives ATP synthase for ATP production, and the second, the Kadenbach mechanism, is focussed on the binding of ATP to Cytochrome c Oxidase (CytOx) at high ATP/ADP ratios, which results in an allosteric conformational change to CytOx, causing inhibition. In times of stress, ATP‐dependent inhibition is switched off and the activity of CytOx is exclusively determined by the membrane potential, leading to an increase in ROS production. The second mechanism for respiratory control depends on the quantity of electron transfer to the Heme aa3 of CytOx. When ATP is bound to CytOx the enzyme is inhibited, and ROS formation is decreased, although the mitochondrial membrane potential is increased. 相似文献
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Jaspreet Kaur Dhanjal Sukriti Goyal Sudhanshu Sharma Rabia Hamid Abhinav Grover 《Biochemical and biophysical research communications》2014
Alzheimer’s is a neurodegenerative disorder resulting in memory loss and decline in cognitive abilities. Accumulation of extracellular beta amyloidal plaques is one of the major pathology associated with this disease. β-Secretase or BACE-1 performs the initial and rate limiting step of amyloidic pathway in which 37–43 amino acid long peptides are generated which aggregate to form plaques. Inhibition of this enzyme offers a viable prospect to check the growth of these plaques. Numerous efforts have been made in recent years for the generation of BACE-1 inhibitors but many of them failed during the preclinical or clinical trials due to drug related or drug induced toxicity. In the present work, we have used computational methods to screen a large dataset of natural compounds to search for small molecules having BACE-1 inhibitory activity with low toxicity to normal cells. Molecular dynamics simulations were performed to analyze molecular interactions between the screened compounds and the active residues of the enzyme. Herein, we report two natural compounds of inhibitory nature active against β-secretase enzyme of amyloidic pathway and are potent lead molecules against Alzheimer’s disease. 相似文献
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A molecular dynamics simulation study of mononuclear iron 15S-lipoxygenase (15S-LOX) from rabbit reticulocytes was performed
to investigate its structure and dynamics; newly developed AMBER force field parameters were employed for the first coordination
sphere of the catalytic iron (II). The results obtained from this study demonstrate that the structural features of the catalytic
iron coordination site are in good agreement with available data obtained from experiments. The motional flexibility of the
N-terminal β-barrel domain is greater than the C-terminal catalytic domain; flexibility was assessed in terms of B-factors and secondary structure calculations. The significant features obtained for the relative motional flexibility of
these two domains of 15S-LOX in solution as well as the isolated C-terminal domain were analyzed in terms of radius of gyration
and maximum diameter, which correlated well with the structural flexibility of 15-lipoxygenase-1 in solution as probed by
small-angle X-ray scattering. The motional flexibility indicates interdomain motion between the N-terminal β-barrel and the
C-terminal catalytic domain; this was further verified by the evaluation of central bending in the solvated LOX molecule,
which identified an unstructured stretch of amino acids as the interdomain linker. The average bending angle confirmed significant
central bending between these two domains, which was linked to the high degree of motional freedom of the N-terminal β-barrel
domain in aqueous solutions. This can be considered to have biological relevance for membrane binding as well as for regulating
the catalytic domain. 相似文献