A beacon of hope in stroke therapy - blockade of pathologically activated cellular events in excitotoxic neuronal death as potential neuroprotective strategies

Hoque, Ashfaqul, Hossain, M. Iqbal, Ameen, S. Sadia, Ang, Ching-Seng, Williamson, Nicholas, Ng, Dominic C. H., Chueh, Anderly C., Roulston, Carli and Cheng, Heung-Chin (2016) A beacon of hope in stroke therapy - blockade of pathologically activated cellular events in excitotoxic neuronal death as potential neuroprotective strategies. Pharmacology and Therapeutics, 160 159-179. doi:10.1016/j.pharmthera.2016.02.009


Author Hoque, Ashfaqul
Hossain, M. Iqbal
Ameen, S. Sadia
Ang, Ching-Seng
Williamson, Nicholas
Ng, Dominic C. H.
Chueh, Anderly C.
Roulston, Carli
Cheng, Heung-Chin
Title A beacon of hope in stroke therapy - blockade of pathologically activated cellular events in excitotoxic neuronal death as potential neuroprotective strategies
Journal name Pharmacology and Therapeutics   Check publisher's open access policy
ISSN 1879-016X
0163-7258
Publication date 2016-04-01
Year available 2016
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.pharmthera.2016.02.009
Open Access Status Not Open Access
Volume 160
Start page 159
End page 179
Total pages 21
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2017
Language eng
Abstract Excitotoxicity, a pathological process caused by over-stimulation of ionotropic glutamate receptors, is a major cause of neuronal loss in acute and chronic neurological conditions such as ischaemic stroke, Alzheimer's and Huntington's diseases. Effective neuroprotective drugs to reduce excitotoxic neuronal loss in patients suffering from these neurological conditions are urgently needed. One avenue to achieve this goal is to clearly define the intracellular events mediating the neurotoxic signals originating from the over-stimulated glutamate receptors in neurons. In this review, we first focus on the key cellular events directing neuronal death but not involved in normal physiological processes in the neurotoxic signalling pathways. These events, referred to as pathologically activated events, are potential targets for the development of neuroprotectant therapeutics. Inhibitors blocking some of the known pathologically activated cellular events have been proven to be effective in reducing stroke-induced brain damage in animal models. Notable examples are inhibitors suppressing the ion channel activity of neurotoxic glutamate receptors and those disrupting interactions of specific cellular proteins occurring only in neurons undergoing excitotoxic cell death. Among them, Tat-NR2B9c and memantine are clinically effective in reducing brain damage caused by some acute and chronic neurological conditions. Our second focus is evaluation of the suitability of the other inhibitors for use as neuroprotective therapeutics. We also discuss the experimental approaches suitable for bridging our knowledge gap in our current understanding of the excitotoxic signalling mechanism in neurons and discovery of new pathologically activated cellular events as potential targets for neuroprotection
Keyword Calpain
Excitotoxicity
Neuron death
NMDAR
NNOS
Stroke
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
 
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