The following grants were approved prior to July 2016
Investigating inflammation in the Alzheimer’s Disease Olfactory Bulb
Investigating early inflammatory changes and their influences in the progression of Alzheimer’s Disease
While the most widely known symptom of Alzheimer’s disease (AD) is short term memory loss, one of the earliest symptoms is often a loss of the sense of smell. This symptom, known as anosmia, is thought to be due to olfactory neuron degeneration or insufficient replacement of olfactory neurons throughout life. Ms Swanson’s research will test the hypothesis that AD pathology is triggered by inflammatory processes in the olfactory bulb by studying post-mortem human brain tissue from the Neurological Foundation Human Brain Bank and using cultured cells. Ultimately, this research will provide insight into early changes occurring in the AD brain which will aid early detection and therapeutic intervention.
Does sAPPα give neuroprotection through its interaction with BACE 1, the enzyme involved in the production of the neurotoxic amyloid β peptide?
Can the interaction of proteins involved in Alzheimer’s disease produce a protective factor?
Late onset Alzheimer’s disease is a growing social and economic burden worldwide and in New Zealand. As yet there are no effective therapies or early intervention treatments. Small soluble aggregates of a peptide are believed to be the toxic species that destroys neurons and impairs memory in Alzheimer’s disease. This peptide is processed from the same large protein as another protein that by contrast restores memory. This neuroprotective protein may bind and inhibit the enzyme that produces the toxic peptide. This project will explore this interaction for the potential of the development of a therapeutic agent or treatment.
Inter-cellular mitochondrial transfer: A cell survival mechanism in response to disease and therapy in neural tissues
The death or survival of brain cells in disease: investigating the biological processes
A striking recent discovery in cell biology is the transfer of mitochondria between cells. Mitochondria are the ‘batteries’ of cells. Mitochondrial transfer has now been shown in a variety of research settings, however the purpose or consequences of this phenomenon are not yet clear. Mr Rowe’s research will examine mitochondrial transfer in two related diseases – neurodegeneration and neurological cancer. Each disease involves the same neural tissues, however the outcomes in each are vastly different - death of the cells in neurodegenerative diseases such as Alzheimer’s, or survival and proliferation of the cells in cancer. This under- explored, likely fundamental biological process has implications for treatment strategies in both neuro-oncology and neurodegeneration.
Non-epileptic seizures in individuals attending neurological services
Examining non-epileptic seizure patient data to better understand symptoms and provide improve clinical services
Psychogenic non-epileptic seizures (PNES) are movements, behaviour or impaired levels of consciousness that appear epileptic in nature but often lack underlying pathophysiological findings, resulting in frequent presentation to hospital settings, misdiagnosis and unnecessary treatments. Though there are no abnormal electrical discharges in the brain, the experience of seizures are real to sufferers, who frequently have no control over these events. The significant distress and daily disruption caused by PNES to patients and their families can be reduced by providing neurologic and psychiatric services better targeting patient’s needs. Key to this is gaining a better understanding of the neurological and psychogenic mechanisms driving PNES. Theses seizures have a high occurrence in hospital settings, with prevalence rates up to 40%. This project aims to assess the frequency of PNES presentations to clinical neurological services at Auckland DHB over a three year period. The symptoms experienced by the patient and any other health concerns will be charted. Potential benefits of the study include gaining a better understanding of symptoms, and providing improved clinical services.
Structure-function studies of ceroid-lipofuscinosis neuronal protein 5 (CLN5)
How do mutations of a gene affect protein function in the brain and cause Batten disease?
Batten disease is a group of severe childhood neurodegenerative conditions for which there is no known cure. The disease is caused by genetic mutations in one of several different ‘CLN’ genes, including CLN5. However, little is known about the normal function of the protein that is programmed by the CLN5 gene. Dr Mace’s study aims to solve the three-dimensional structure of the CLN5 protein, so as to understand how mutations in the CLN5 gene perturb protein function and cause Batten disease. This may also provide a template for future therapies that directly target the CLN5 protein.