Novel diagnostic and therapeutic targets in ischaemic brain injury
MicroRNA as Novel Diagnostic biomarkers in stroke (MiND)
Ischaemic stroke is a leading cause of death and major disability resulting from death of brain tissue and focal neurological deficits; however, despite decades of research, treatment options remain limited and the lack of therapeutic treatment strategies is a critical clinical problem. To this end, there is a need for biomarkers as clinically useful diagnostic and prognostic indicators for outcome in patients, improving functional recovery through individualised therapeutic strategies. Such biomarkers have potential to be developed into neuroprotective agents aimed at rescuing ischaemic neurons from irreversible injury, widening the therapeutic window, improving neurological outcome and facilitating brain recovery. Endogenous microRNAs (miRNA) are potent regulators of gene function elevated in a wide range of diseases, with crucial roles as regulators of signalling pathways involved in ischaemia-reperfusion injury.
The overall aim of this research programme is to examine the unique molecular profile present in blood samples from patients suffering ischaemic stroke and to examine the relationship between these blood biomarkers and clinical outcome. This will identify a unique molecular signature associated with ischaemic stroke and provide invaluable information for the development of specific miRNA as clinically relevant diagnostic and prognostic blood biomarkers. Furthermore, identification of potential therapeutic targets has significant potential for better success in the development and translation of novel neuroprotective agents to limit progressive neuronal damage and death in the ischaemic penumbra.
Areas of interest:
Activation of AMP-activated protein kinase (AMPK), a key protein kinase activated in response to various physiological or pathological stimuli such as ischemia, hypoxia and glucose deprivation, is a critical regulator in cellular energy function in response to stress. The pro-survival or pro-apoptotic effect of AMPK activation is determined by the duration and level of the AMPK activity following energetic stress and the extent of recovery of ATP depletion and cellular bioenergetics, determining whether a cell can tolerate a stimulus or initiates cell death. To this end, Dr. Pfeiffer’s research focuses on the elucidation of the molecular signatures mediating the effects of AMPK activation to provide insight into the functional relevance and identification of individual regulatory targets, including microRNA.
Identification of elevated microRNA in response to progressive neuronal injury may identify ischaemia-associated miRNAs as important targets for development as biomarkers and therapeutics in the clinical management of ischaemic brain injury. The aim of this research is to characterise and validate such microRNA in both pre-clinical and clinical settings.