P7C3-A20 neuroprotection is independent of Wallerian degeneration in Primary Neuronal Culture
Publication Date
2018-12-12Journal Title
NeuroReport
ISSN
0959-4965
Publisher
Wolters Kluwer Health
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Hill, C., Menon, D., & Coleman, M. (2018). P7C3-A20 neuroprotection is independent of Wallerian degeneration in Primary Neuronal Culture. NeuroReport https://doi.org/10.1097/WNR.0000000000001146
Abstract
The anti-apoptotic, neuroprotective compound P7C3-A20 reduces neurological deficits when administered to murine in vivo models of traumatic brain injury. P7C3-A20 is thought to exert its activity through small-molecule activation of the enzyme nicotinamide phosphoribosyltransferase (NAMPT). This enzyme converts nicotinamide to nicotinamide mononucleotide (NMN), the precursor to nicotinamide adenine dinucleotide (NAD) synthesis. Alterations to this bioenergetic pathway have been shown to induce Wallerian degeneration of the distal neurite following injury. This study aimed to establish whether P7C3-A20, through induction of NAMPT activity, would affect the rate of Wallerian degeneration. The model systems used were dissociated primary cortical neurons, dissociated superior cervical ganglion neurons, and superior cervical ganglion explants. P7C3-A20 failed to demonstrate any protection against Wallerian degeneration induced by neurite transection or vincristine administration. Furthermore, there was a concentration dependent neurotoxicity. These findings are important in understanding the mechanism by which P7C3-A20 mediates its effects- a
key step before moving to human clinical trials.
Sponsorship
Wellcome Trust
Funder references
European Commission (602150)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1097/WNR.0000000000001146
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286268
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