Deciphering the role of c-Src tyrosine kinase in excitotoxic neuronal death during ischemic stroke


Project Details

An ischemic stroke occurs when the one of the blood vessels supplying the brain (e.g. the middle cerebral artery) is blocked, causing damage to the adjacent neurons. The damaged neurons induce a second round of neuronal death by secreting an excessive quantity of the neurotransmitter glutamate.

Over-stimulation of glutamate receptors in the neighbouring viable neurons causes them to undergo cell death – a process known as excitotoxicity (Figure 1). Exactly how over-stimulation of glutamate receptors induces neuronal death is poorly understood.

photomicrograph of treated and untreated neurons

Figure 1: Over-stimulation of glutamate receptors induces cell death of cultured primary cortical neurons. The viable neurons are stained with Calcein-AM (green) and the damaged neurons are stained with Ethidium homodimer-1 (red). To induce cell death, neurons were treated with 100 μM glutamate for 8 h.

Results of studies by ourselves and others have indicated that inhibitors of c-Src kinase are protectants, indicating that aberrant activation and/or subcellular localisation of c-Src contribute to excitotoxic neuronal death.

We are using cultured mouse primary cortical neurons and a rat model of ischemic stroke to decipher how c-Src is aberrantly activated in neurons undergoing excitotoxic neuronal death and how the activated c-Src induces premature death of neurons. We have demonstrated that c-Src is essential for neuronal survival under physiological condition. However, in neurons over-stimulated with glutamate, c-Src is aberrantly modified and activated. This aberrantly modified form of c-Src then directs neurons to undergo cell death. We are currently studying the structure and function of this aberrantly modified form of c-Src.

Research Group

Cheng laboratory: Molecular enzymology of protein kinases and phosphatases involved in human diseases

Faculty Research Themes


School Research Themes

Cancer in Biomedicine, Molecular Mechanisms of Disease, Cell Signalling

Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Biochemistry and Molecular Biology

Unit / Centre

Cheng laboratory: Molecular enzymology of protein kinases and phosphatases involved in human diseases

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