Cellular Neurodegeneration Laboratory
Pathological mechanisms affecting neurons and astrocytes, which have an interdependent relationship essential to brain health, are the focus of our laboratory. Diverse experimental approaches provide insights into how new strategies may be targeted to rescue threatened neurones and to establish a supportive environment near an injury zone.
Ageing or injured neurones accumulate damaged molecules and organelles which affect their function. This process is termed autophagy (“self-eating”) and represents one of the cellular rubbish removal mechanisms. If the load becomes too extreme or if the autophagic mechanisms become compromised, the process can become a form of programmed cell death. Most research into the controlling mechanisms has been performed in non-mammalian cells, so our work in primary neurones is groundbreaking. Damaged mitochondria also enter the autophagic cascade through a process termed mitophagy. We have found that disturbed energy generation causes mitochondria to lose their membrane potential with a concomitant drop in ATP production and entry into mitophagy. Since disturbed energetics underpins various forms of neurodegeneration, we believe that this cascade contributes to many degenerative conditions. We are currently investigating autophagy in other brain injury models.
Over many years our team has studied the neurobiology of astrocytes and made impressive advances in defining “good” or “bad” responses which relate to the state of inflammation in brain patholgies. By culturing mature astrocyes in 3D on bioscaffolds, we found a healthy astrocytic phenotype displaying reduced GFAP, and increased G-actin, glutamate transport, brain-derived trophic factor (BDNF) and anti-oxidant activity. These “signposts” guide current studies where a novel bioscaffold presenting sugar moieties has shown promise in minimising inflammation in studies performed in cultured astrocytes and in vivo in model of traumatic brain injury. The ultimate goal is a safe, bio-injectable to prevent untoward glial scarring and to promote regeneration.
A glimpse at our researchBioengineered 3D astrocytes to reveal healthy biology and neurotherapeutic targets
Scientists in the Neurodegeneration division interrogate how neurones live, die and can be rescued to improve brain function in degenerative conditions such as Parkinson’s and Motor Neuron Diseases. There is no effective treatment for Motor Neurone Disease and the incidence of Parkinson’s Disease is rising alarmingly in our aging community. Gene abnormalities, energy deprivation, toxic rubbish accumulation and inflammation all contribute to a toxic environment for brain cells. Our teams study these events in animal models and cultured cells, with a view to translating knowledge into new therapies for human patients.