Quick Project Snapshot
The role of tau protein in olfactory processes
The structural protein tau is implicated in a number of debilitating neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease (PD). Recent literature suggest that mice deficient in tau share some similarities with PD, and indeed our laboratory’s investigations indicate that loss of tau protein increases the level of insoluble, aggregated alpha-synuclein (α-syn) in the brain. This protein is implicated in PD as a genetic cause, risk factor and the primary constituent of Lewy bodies, a histopathological hallmark of PD that spreads across the brain with disease progression. In addition to the characteristic, devastating impairments in the locomotor system, one of the earliest symptoms of PD is an impairment in the sense of smell (olfaction), which may be an early predictor of PD. In this study, we will examine the olfactory phenotype of mice deficient in tau, including behavioural examinations (odour detection, discrimination and memory) and protein biochemistry of the olfactory bulb. The project may be expanded to include examination of olfaction and biochemistry in a tau transgenic overexpression mouse line. Skills gained will include behavioural testing in mice and Western blotting techniques.
This laboratory has expertise in Medicinal Chemistry (in association with Prana Biotechnology) and in biomarker discovery. More recently, it has focussed on the pathways leading to Parkinson’s disease, especially around the oxidative modifications of tau.
The Australian Imaging, Biomarker and Lifestyle (AIBL) Study, the Dementia Collaborative Research Centres (DCRC) and the Cooperative Research Centre for Mental Health (CRCMH). AIBL, DCRC and the CRCMH are intimately involved in our research programs, relying on patient cohorts for biomarker and imaging discovery in both neurodegenerative and psychotic illness.
Translation of our research findings into clinical practice will become more important over the next five years, as we move from a series of failed or equivocal phase 3 drug trials sponsored by the pharmaceutical industry. There is now general agreement that these drug trials need to be based at the earliest possible stage of Alzheimer’s disease, hence our participation in the Dominantly Inherited Alzheimer Network (DIAN) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (the A4 study). These two pre-clinical trials are designed to administer drugs in the preclinical phases of both familial and sporadic Alzheimer’s disease.
All Projects by this LabEffect of Abeta on excitotoxic signalling pathwaysEffect of tau phosphorylation on exosome release in cell culture systemsThe influence of alpha-synuclein on olfactionThe role of peroxinitrite in depressionThe role of tau protein in olfactory processesAre exosomes driving Alzheimer’s disease pathogenesis?Discovering how toxic proteins traffic from cell to cell in Alzheimer’s disease.Uncovering the role of exosome derived lipids in Alzheimer’s disease.
Dr Lachlan Thompson
Prof David Finkelstein
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.