المؤلفون: Congheng Chen, Yu Ding, Juan Zhao, Qingnan Liang, Qing Sun, Ping Zhou, Yuan Zhang, Lihui Xu

المصدر: Journal of neurochemistry. 143(1)

مصطلحات موضوعية: 0301 basic medicine, Amyloid, Stereochemistry, Cell Survival, Protein Conformation, Fibril, Biochemistry, Metal Chelator, Ferric Compounds, PC12 Cells, Catechin, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, medicine, Animals, Chelation, Chelating Agents, Fibrillation, Transition (genetics), Cell Death, Dose-Response Relationship, Drug, Chemistry, food and beverages, Gallate, Rats, 030104 developmental biology, Cytoprotection, Toxicity, Biophysics, alpha-Synuclein, medicine.symptom, Reactive Oxygen Species, 030217 neurology & neurosurgery

الوصف: The fibrillation and aggregation of α-synuclein (AS), along with the conformational transition from random coil to β-sheet, are the critical steps in the development of Parkinson's disease (PD). It is acknowledged that iron accumulation in the brain may lead to the fibrillation of AS. However, (-)-epigallocatechin gallate (EGCG) can penetrate the blood-brain barrier, chelate metal ions, and inhibit the fibrillation of amyloid proteins. Therefore, EGCG is warranted to be investigated for its potential to cure amyloid-related diseases. In the present work, we sought to study the effects of EGCG on Fe(III)-induced fibrillation of AS on both molecular and cellular levels. We demonstrate that Fe(III) interacts with the amino residue of Tyr and Ala of AS, then accelerates the fibrillation of AS, and increases intracellular reactive oxygen species (ROS) in the AS transduced-PC12 cells (AS-PC12 cells). However, EGCG significantly inhibits this process by chelating Fe(III) and protects AS-PC12 cells against the toxicity induced by ROS and β-sheet-enriched AS fibrils. These findings yield useful information that EGCG might be a promising drug to prevent and treat the neurodegenerative diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53314fa9b1baa3e3d9d51251a00face1Test
https://pubmed.ncbi.nlm.nih.gov/28792609Test

المؤلفون: Ishrut Hussain, Lit-Fui Lau, Zehong Wan, Yu Ding, Liang Ye, Yunhong Huang, Adrian Hall, Ting Li, Na Rong, Ziqiang Cheng, Yasuji Matsuoka, Jinqiang Zhang, Xiu-Juan Yang, Daniel Hong Seng Lee, David C. Harrison, Shiyi Jin

المصدر: Journal of Neurochemistry. 121:277-286

مصطلحات موضوعية: Alanine, biology, Stereochemistry, Chemistry, Notch signaling pathway, Cleavage (embryo), Biochemistry, Cell biology, Cellular and Molecular Neuroscience, Cell culture, Amyloid precursor protein, biology.protein, γ secretase, Signal transduction, Amyloid precursor protein secretase

الوصف: γ-secretase inhibitors (GSIs) have been developed to reduce amyloid-β (Aβ) production for the treatment of Alzheimer's disease by inhibiting the cleavage of amyloid precursor protein (APP). However, cross-inhibitory activity on the processing of Notch can cause adverse reactions. To avoid these undesirable effects, γ-secretase modulators (GSMs) are being developed to selectively reduce toxic Aβ production without perturbing Notch signaling. As it is also known that GSIs can cause a paradoxical increase of plasma Aβ over the baseline after a transient reduction (known as Aβ-rebound), we asked if GSMs would cause a similar rebound and what the potential mechanism might be. Our studies were performed with one GSI (LY-450139) and two chemically distinct GSMs. Although LY-450139 caused Aβ-rebound as expected in rat plasma, the two GSMs did not. Inhibition of APP processing by LY-450139 induced an accumulation of γ-secretase substrates, α- and β-C-terminal fragments of APP, but neither GSM caused such an accumulation. In conclusion, we discover that GSMs, unlike GSIs, do not cause Aβ-rebound, possibly because of the lack of accumulation of β-C-terminal fragments. GSMs may be superior to GSIs in the treatment of Alzheimer's disease not only by sparing Notch signaling but also by avoiding Aβ-rebound.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::25443e9a96506c60522dff2ec56a3168Test
https://doi.org/10.1111/j.1471-4159.2011.07560.xTest

المؤلفون: Zhi-Hong Zhang, Yu Ding, Yu-Qiu Zhang, Wen-Hua Ren, Yan-Ai Mei, Song Jiao, Zheng Liu

المصدر: Journal of Neurochemistry. 100:979-991

مصطلحات موضوعية: medicine.medical_specialty, Small interfering RNA, Patch-Clamp Techniques, Protein subunit, Apoptosis, Biology, Transfection, Biochemistry, Membrane Potentials, Potassium Chloride, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Shab Potassium Channels, Cerebellum, Internal medicine, Cyclic AMP, medicine, Animals, Gene silencing, Drug Interactions, Enzyme Inhibitors, RNA, Small Interfering, Protein kinase A, Cells, Cultured, Neurons, Forskolin, Dose-Response Relationship, Drug, Reverse Transcriptase Polymerase Chain Reaction, Colforsin, Dose-Response Relationship, Radiation, Cyclic AMP-Dependent Protein Kinases, Electric Stimulation, Hedgehog signaling pathway, Rats, Cell biology, medicine.anatomical_structure, Endocrinology, Animals, Newborn, chemistry, Neuron

الوصف: Previously, we have reported that apoptosis of cerebellar granular neurons induced by incubation in 5 mm K(+) and serum-free medium (LK-S) was associated with an increase in the delayed rectifier K(+) current (I(K)). Here, we show that I(K) associated with apoptotic neurons is mainly encoded by a Kv2.1 subunit. Silencing Kv2.1 expression by small interfering RNA reduces I(K) and increases neuron viability. Forskolin is able to decrease the I(K) amplitude recording from neurons of both the LK-S and control group, and prevents apoptosis of granule cells that are induced by LK-S. Dibutyryl cAMP mimicks the effect of forskolin on the modulation of I(K) and, accordingly, the inhibitor of protein kinase A, H-89, aborts the neuron-protective effect induced by forskolin. Whereas the expression of Kv2.1 was silenced by Kv2.1 small interfering RNA, the inhibition of forskolin on the current amplitude was significantly reduced. Quantitative RT-PCR and whole-cell recording revealed that the expression of Kv2.1 was elevated in the apoptotic neurons, and forskolin significantly depressed the expression of Kv2.1. We conclude that the protection against apoptosis via the protein kinase A pathway is associated with a double modulation on I(K) channel properties and its expression of alpha-subunit that is mainly encoded by the Kv2.1 gene.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3ca82f0a5e6c892c16be55eb1d53a1baTest
https://doi.org/10.1111/j.1471-4159.2006.04261.xTest

المؤلفون: Ting, Li, Yunhong, Huang, Shiyi, Jin, Liang, Ye, Na, Rong, Xiujuan, Yang, Yu, Ding, Ziqiang, Cheng, Jinqiang, Zhang, Zehong, Wan, David C, Harrison, Ishrut, Hussain, Adrian, Hall, Daniel Hong Seng, Lee, Lit-Fui, Lau, Yasuji, Matsuoka

المصدر: Journal of neurochemistry. 121(2)

مصطلحات موضوعية: Male, Neurons, Alanine, Amyloid beta-Peptides, Receptors, Notch, Mice, Transgenic, Plaque, Amyloid, Azepines, Peptide Fragments, Cell Line, Rats, Rats, Sprague-Dawley, Mice, Area Under Curve, Animals, Humans, Amyloid Precursor Protein Secretases, Enzyme Inhibitors, Cells, Cultured, Chromatography, High Pressure Liquid, Signal Transduction

الوصف: γ-secretase inhibitors (GSIs) have been developed to reduce amyloid-β (Aβ) production for the treatment of Alzheimer's disease by inhibiting the cleavage of amyloid precursor protein (APP). However, cross-inhibitory activity on the processing of Notch can cause adverse reactions. To avoid these undesirable effects, γ-secretase modulators (GSMs) are being developed to selectively reduce toxic Aβ production without perturbing Notch signaling. As it is also known that GSIs can cause a paradoxical increase of plasma Aβ over the baseline after a transient reduction (known as Aβ-rebound), we asked if GSMs would cause a similar rebound and what the potential mechanism might be. Our studies were performed with one GSI (LY-450139) and two chemically distinct GSMs. Although LY-450139 caused Aβ-rebound as expected in rat plasma, the two GSMs did not. Inhibition of APP processing by LY-450139 induced an accumulation of γ-secretase substrates, α- and β-C-terminal fragments of APP, but neither GSM caused such an accumulation. In conclusion, we discover that GSMs, unlike GSIs, do not cause Aβ-rebound, possibly because of the lack of accumulation of β-C-terminal fragments. GSMs may be superior to GSIs in the treatment of Alzheimer's disease not only by sparing Notch signaling but also by avoiding Aβ-rebound.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::79a665d0671a0c56e8265f0b17079561Test
https://pubmed.ncbi.nlm.nih.gov/22035227Test

المؤلفون: Song Jiao, Zheng Liu, Wen-Hua Ren, Yu Ding, Yu-Qiu Zhang, Zhi-Hong Zhang, Yan-Ai Mei

المصدر: Journal of Neurochemistry; Feb2007, Vol. 100 Issue 4, p979-991, 13p, 2 Color Photographs, 2 Black and White Photographs, 1 Diagram, 1 Chart, 7 Graphs

مصطلحات موضوعية: NERVOUS system, APOPTOSIS, PROTEIN kinases, PHOSPHOTRANSFERASES, CELL death

مستخلص: Previously, we have reported that apoptosis of cerebellar granular neurons induced by incubation in 5 mm K⁺ and serum-free medium (LK-S) was associated with an increase in the delayed rectifier K⁺ current ( IK). Here, we show that IK associated with apoptotic neurons is mainly encoded by a Kv2.1 subunit. Silencing Kv2.1 expression by small interfering RNA reduces IK and increases neuron viability. Forskolin is able to decrease the IK amplitude recording from neurons of both the LK-S and control group, and prevents apoptosis of granule cells that are induced by LK-S. Dibutyryl cAMP mimicks the effect of forskolin on the modulation of IK and, accordingly, the inhibitor of protein kinase A, H-89, aborts the neuron-protective effect induced by forskolin. Whereas the expression of Kv2.1 was silenced by Kv2.1 small interfering RNA, the inhibition of forskolin on the current amplitude was significantly reduced. Quantitative RT-PCR and whole-cell recording revealed that the expression of Kv2.1 was elevated in the apoptotic neurons, and forskolin significantly depressed the expression of Kv2.1. We conclude that the protection against apoptosis via the protein kinase A pathway is associated with a double modulation on IK channel properties and its expression of α-subunit that is mainly encoded by the Kv2.1 gene. [ABSTRACT FROM AUTHOR]

: Copyright of Journal of Neurochemistry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Gatley, S. John, Yu, Ding-Wei, Fowler, Joanna S., MacGregor, Robert R., Schlyer, David J., Dewey, Stephen L., Wolf, Alfred P., Martin, Thomas, Shea, Colleen E., Volkow, Nora D.

المصدر: Journal of Neurochemistry; Mar1994, Vol. 62 Issue 3, p1154-1162, 9p