Quick Project Snapshot
The influence of alpha-synuclein on olfaction
Parkinson’s disease (PD) is a devastating neurodegenerative disorder. In addition to the characteristic 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. Our laboratory studies the role of alpha synuclein (α-syn) in PD, a protein 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. This project aims to characterise olfaction deficits in a new mouse mode of PD pathology, whereby we track propagation of pathological changes in the mouse brain after the injection of α-syn fibrils. Our initial data show impairment of odour detection in this model, a feature highly relevant to PD. Methods used in this project will include stereotaxic surgery and bromodeoxyuridine marking of new neurons to investigate the influence of α-syn fibrils on neurogenesis and the migration of new neurons to the olfactory bulb, in order to determine whether these processes are influenced in α-syn-induced olfactory deficits. An extension of the project may include examination of the integration and synaptic complexity of new neurons, and the impact of α-syn on the parallel vomeronasal/social odour olfactory system. Skills learned will include stereotaxic surgery, animal behaviour testing, Western blotting techniques and immunohistochemistry.
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.