Parkinsons Melb Uni

White Laboratory

Contact:	Associate Professor Anthony White
Phone:	+61 3 8344 1805
Fax:	+61 3 8344 4004
Email:	arwhite@unimelb.edu.au

The White laboratory studies the role of biometals such as copper (Cu), zinc (Zn) and iron (Fe) in neurodegenerative diseases. These metals have important roles in normal cell functions. However, abnormal biometal metabolism is central to a number of neurodegenerative illnesses including Alzheimer's disease, Parkinson's disease, motor neuron disease and prion disorders. Recent studies have shown that pharmacological modulation of biometal homeostasis in the brain may offer a novel therapeutic approach to treating these brain diseases. An important step in developing these novel drugs is to obtain a clear understanding of how biometals affect neuronal metabolism and synaptic function. Our laboratory is investigating the role of biometals in neuronal cell signaling pathways. We are also developing and testing novel neuroprotective metallo-complexes that may restore brain function in neurodegenerative diseases.

Key research areas are:

Investigating how biometals control neuronal cell signaling pathways

Biometals are central to the pathology of many brain diseases, however, little is known about the normal function of metals such as Cu and Zn in neuronal cell signaling pathways. These pathways affect neuronal survival and synaptic function and are important targets for therapeutic intervention in neurodegeneration. It is critical to obtain a greater understanding of how biometals modulate cell signaling during normal brain function and in disease. We are currently investigating how Cu and Zn control a number of different cell signaling pathways including PI3K, GSK3 and MAPK pathways and how age-related changes to these pathways contribute to neurodegenerative diseases.

 

Development of neuroprotective metallo-complexes Together with collaborators at the Department of Pathology and Bio21 Institute, we have identified a class of neuroprotective cell permeable metallo-complexes (bis(thiosemicarbazonato)-metal complexes or BTSCs). These small molecules cross the blood brain barrier and enter neurons and glia. Delivery of small levels of Cu or Zn can be modulated by structural changes to the complexes. These metallo-compounds offer exciting potential as a novel therapeutic strategy for treating neurodegenerative diseases. Release of the metals activates neuroprotective signaling cascades resulting in significant improvements in multiple animal models of neurodegeneration including Alzheimer’s disease, Parkinson’s disease and motor neuron disease. We are currently using cell culture and animal models to investigate the uptake, metal release and activation of neuroprotective pathways of these important compounds with the aim of moving the compounds into pre-clinical testing for treatment of neurodegeneration.
This project was identified by the National Health and Medical Research Council of Australia (NH&MRC) as one of the Top Ten Research Projects funded in 2010. http://www.nhmrc.gov.au/guidelines/publications/r48

 Ther release

Potential Strategy To Restore Motor And Cognitive Function In Parkinson's Disease

Main Category: Parkinson's Disease
Also Included In: Radiology / Nuclear Medicine
Article Date: 04 Apr 2012 - 1:00 PDT

An agent under consideration for use in PET imaging combats neuronal death to relieve Parkinsonian symptoms in animal models, according to a study published in the Journal of Experimental Medicine.

The movement-related symptoms of Parkinson's disease, including muscle rigidity and tremors, are caused by the loss of dopamine-secreting neurons in the brain. Current therapies aim at increasing and maintaining dopamine levels to correct these motor impairments. However, these approaches do not address the underlying neuronal death that initiated the disease.

David Finkelstein, Kevin Barnham, and colleagues at the University of Melbourne find that the PET imaging agent CuII(atsm) reverses the neurotoxicity that destroys dopamine-secreting neurons. Improvements in motor skills and memory were observed after treatment in four unique animal models of Parkinson's disease. The authors suggest this compound functions as a scavenger of peroxynitrite, whose accumulation is known to promote neuronal death.

These results point to a potential strategy to restore motor and cognitive function in Parkinson's disease patients by reviving neuronal function rather than solely masking symptoms.