The Experts below are selected from a list of 6 Experts worldwide ranked by ideXlab platform

Edwin B George - One of the best experts on this subject based on the ideXlab platform.

  • axotomy induced axonal degeneration is mediated by calcium influx through ion specific channels
    The Journal of Neuroscience, 1995
    Co-Authors: Edwin B George, Jonathan D Glass, John W Griffin
    Abstract:

    We examined the role of extracellular calcium entry, the possible involvement of axonal calcium channels, and the potential protective effect of calcium channel and calpain antagonists in axotomy-induced axonal degeneration using murine dorsal root ganglia in cell culture. We found that calcium entry is both necessary and sufficient to induce axonal degeneration after axotomy, and may be inhibited by cobalt, manganese, dihydropyridines, and bepridil. Tetrodotoxin and omega- conotoxin are ineffective in preventing axonal degeneration. The activation of calpains also appears to be necessary and sufficient for axonal degeneration to proceed, and can be blocked with membrane- permeant leupeptin analogs and the oxirane Aloxistatin. Although other calcium-activated events may occur, it appears that inhibition of calpain is sufficient to preserve the axon at the light microscope level, and to prevent axonal cytoskeleton degradation as detected by immunofluorescent staining. Our results suggest that axonal degeneration after axotomy involves the following sequence of events: (1) a lag-period after axotomy prior to the onset of axonal degeneration, (2) entry of calcium into the axon through an intact axolemma via a calcium-specific ion transport mechanism, (3) activation of calcium-dependent effector molecules such as calpains, (4) degradation of the axonal cytoskeleton. The details of the second step require further elucidation, and are of particular interest because this step is a potential target for therapies directed towards peripheral neuropathies.

Jonathan D Glass - One of the best experts on this subject based on the ideXlab platform.

  • axotomy induced axonal degeneration is mediated by calcium influx through ion specific channels
    The Journal of Neuroscience, 1995
    Co-Authors: Edwin B George, Jonathan D Glass, John W Griffin
    Abstract:

    We examined the role of extracellular calcium entry, the possible involvement of axonal calcium channels, and the potential protective effect of calcium channel and calpain antagonists in axotomy-induced axonal degeneration using murine dorsal root ganglia in cell culture. We found that calcium entry is both necessary and sufficient to induce axonal degeneration after axotomy, and may be inhibited by cobalt, manganese, dihydropyridines, and bepridil. Tetrodotoxin and omega- conotoxin are ineffective in preventing axonal degeneration. The activation of calpains also appears to be necessary and sufficient for axonal degeneration to proceed, and can be blocked with membrane- permeant leupeptin analogs and the oxirane Aloxistatin. Although other calcium-activated events may occur, it appears that inhibition of calpain is sufficient to preserve the axon at the light microscope level, and to prevent axonal cytoskeleton degradation as detected by immunofluorescent staining. Our results suggest that axonal degeneration after axotomy involves the following sequence of events: (1) a lag-period after axotomy prior to the onset of axonal degeneration, (2) entry of calcium into the axon through an intact axolemma via a calcium-specific ion transport mechanism, (3) activation of calcium-dependent effector molecules such as calpains, (4) degradation of the axonal cytoskeleton. The details of the second step require further elucidation, and are of particular interest because this step is a potential target for therapies directed towards peripheral neuropathies.

John W Griffin - One of the best experts on this subject based on the ideXlab platform.

  • axotomy induced axonal degeneration is mediated by calcium influx through ion specific channels
    The Journal of Neuroscience, 1995
    Co-Authors: Edwin B George, Jonathan D Glass, John W Griffin
    Abstract:

    We examined the role of extracellular calcium entry, the possible involvement of axonal calcium channels, and the potential protective effect of calcium channel and calpain antagonists in axotomy-induced axonal degeneration using murine dorsal root ganglia in cell culture. We found that calcium entry is both necessary and sufficient to induce axonal degeneration after axotomy, and may be inhibited by cobalt, manganese, dihydropyridines, and bepridil. Tetrodotoxin and omega- conotoxin are ineffective in preventing axonal degeneration. The activation of calpains also appears to be necessary and sufficient for axonal degeneration to proceed, and can be blocked with membrane- permeant leupeptin analogs and the oxirane Aloxistatin. Although other calcium-activated events may occur, it appears that inhibition of calpain is sufficient to preserve the axon at the light microscope level, and to prevent axonal cytoskeleton degradation as detected by immunofluorescent staining. Our results suggest that axonal degeneration after axotomy involves the following sequence of events: (1) a lag-period after axotomy prior to the onset of axonal degeneration, (2) entry of calcium into the axon through an intact axolemma via a calcium-specific ion transport mechanism, (3) activation of calcium-dependent effector molecules such as calpains, (4) degradation of the axonal cytoskeleton. The details of the second step require further elucidation, and are of particular interest because this step is a potential target for therapies directed towards peripheral neuropathies.

Kleemiss Florian - One of the best experts on this subject based on the ideXlab platform.

  • Similarities and differences between crystal and enzyme environmental effects on the electron density of drug molecules
    'Wiley', 2021
    Co-Authors: Kleemiss Florian, Wieduwilt, Erna K., Hupf Emanuel, Shi, Ming W., Stewart, Scott G., Jayatilaka Dylan, Turner, Michael J., Sugimoto Kunihisa, Nishibori Eiji, Schirmeister Tanja
    Abstract:

    The crystal interaction density is generally assumed to be a suitable measure of the polarization of a low‐molecular weight ligand inside an enzyme, but this approximation has seldomly been tested and has never been quantified before. In this study, we compare the crystal interaction density and the interaction electrostatic potential for a model compound of loxistatin acid (E64c) with those inside cathepsin B, in solution and in vacuum. We apply QM/MM calculations and experimental quantum crystallography to show that the crystal interaction density is indeed very similar to the enzyme interaction density. Less than 0.1e are shifted between these two environments in total. However, this has non‐negligible consequences for derived properties

Wieduwilt, Erna K. - One of the best experts on this subject based on the ideXlab platform.

  • Similarities and differences between crystal and enzyme environmental effects on the electron density of drug molecules
    'Wiley', 2021
    Co-Authors: Kleemiss Florian, Wieduwilt, Erna K., Hupf Emanuel, Shi, Ming W., Stewart, Scott G., Jayatilaka Dylan, Turner, Michael J., Sugimoto Kunihisa, Nishibori Eiji, Schirmeister Tanja
    Abstract:

    The crystal interaction density is generally assumed to be a suitable measure of the polarization of a low‐molecular weight ligand inside an enzyme, but this approximation has seldomly been tested and has never been quantified before. In this study, we compare the crystal interaction density and the interaction electrostatic potential for a model compound of loxistatin acid (E64c) with those inside cathepsin B, in solution and in vacuum. We apply QM/MM calculations and experimental quantum crystallography to show that the crystal interaction density is indeed very similar to the enzyme interaction density. Less than 0.1e are shifted between these two environments in total. However, this has non‐negligible consequences for derived properties