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SANI - South Australian
Neuroscience Institute
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Parkinson and Alzheimer Disease Laboratory

We are interested in the physical basis of neurodegeneration in human brains with special concerns for Parkinson’s and Alzheimer’s related diseases. Our laboratory has three complementary lines of research:

  • Neuropathology and Neurobiology
  • Neuroproteomics
  • Oxidative Stress and Neuroprotection

Each consists of multiple specific question focused projects. All our projects are centred on perceptions of interests and importance to neurodegenerative mechanisms, drawn primarily from in-house anatomical and chemical examinations of post-mortem human brain material of patients who died from Parkinson, Alzheimer or other neurodegenerative diseases obtained through the South Australian Brain Bank and Australian Tissue Bank Consortium. The South Australian Brain Bank also runs the South Australian Brain Tissue Donor Program and is executed by Ms Robyn Flook based at Flinders Medical Centre.

Neuropathology / Neurobiology: We have a long standing interest in systematically documenting cellular and subcellular pathologies in brains of Parkinson’s, Alzheimer’s and other neurodegenerative diseases. We use a range of immunological labelling (immunohistology, immunoblotting) and detecting (light, electron, atomic force imaging) techniques combined with molecular markers for generic or specific biological and pathogenic processes relevant to neurodegeneration, for example, alpha-synuclein for Lewy bodies and related pathologies in Parkinson’s disease, beta-amyloid and tau proteins for Alzheimer’s disease specific pathologies. In parallel, we use various in vitro systems (isolated proteins, cell organelles, cell cultures) to replicate aspects of pathologies observed in diseased human brains as models, to test derived hypotheses or dissect key steps of biological or cellular processes perceived to play a role in neurodegeneration in the disease.

Neuroproteomics: We isolate disease specific abnormal proteins, protein complexes or inclusion bodies from brain tissues with various neurodegenerative diseases (Lewy bodies of Parkinson’s disease, oligodendroglial inclusions of multiple system atrophy, ubiquitinated proteins in aged brain) and identify the physical nature of the abnormalities and characterize their potential role in disease pathogensis, their value for diagnosis, treatment and prevention of neurodegenerative diseases. We currently focus on establishing and developing alpha-synuclein based diagnostics for Parkinson’s and related diseases.

Oxidative Stress / Neuroprotection: We are mapping the cellular distribution of the peroxiredoxin family and other antioxidant enzymes in the human brain and determining their association with Parkinson's and Alzheimer's disease pathology. We have also isolated a GPx/alpha-synuclein aggregation isolated from Parkinson's disease brain tissue and are determining if this is either chaperone mediated autophagy or endoplasmic reticulum trafficking vesicles from the endoplasmic reticulum to the Golgi apparatus. This is a significant finding as this could indicate how Lewy bodies form or give incite into a mechanism of Lewy body degradation. We are also determining the specific pattern of toxic and oxidative damage in human brain tissue using oxidative stress biomarkers and determining if this can be replicated in a human neuronal cell. Using this same model we determining if these toxic insults result the upregulation of cellular antioxidant enzymes.

Investigators

Neuropathology / Neurobiology: Wei Ping Gai, MB, MSc, PhD

Neuroproteomics: Tim Chataway, BSc(Hons), PhD

Oxidative Stress / Neuroprotection: John Power, BSc(Hons), PhD

Visiting Research Fellows / Scholar

Dr Feng Guo, PhD, China

Support Staff

Fariba Chegini, BSc(Hons), Research Assistant

Students

JianQun Gao, Master of Science By Research Student

Contacts

Neuropathology / Neurobiology Neuroproteomics Oxidative Stress / Neuroprotection
Dr Wei Ping Gai Dr Tim Chataway Assoc Prof John Power

Ph: (08) 8204 6439
Int Ph: +61 8 8204 6439
Fax: (08) 8204 5768
Int Fax: +61 8 8204 5768
Email: weiping.gai@flinders.edu.au
University Profile Page

Ph: (08) 8204 3108
Int Ph: +61 8 8204 3108
Fax: (08) 8204 5768
Int Fax: +61 8 8204 5768
Email: tim.chataway@flinders.edu.au
University Profile Page
Ph: (08) 8204 4240
Int Ph: +61 8 8204 4240
Fax: (08) 8204 5768
Int Fax: +61 8 8204 5768
Email: john.power@flinders.edu.au
University Profile Page
 

Research Projects

Collaborative Research

Neuropathology / Neurobiology;

Prof Heiko Braak, Dept of Clinical Neuroanatomy, The JW Goethe University, Frankfurt, Germany: Human Brain Anatomy and Pathology.

Prof Poul Henning Jensen, Dept of Medical Biochemistry, Universe of Aarhus, Denmark: Alpha-Synuclein-Interacting Proteins in Neurogenerative Disease.

Assoc Prof Michael Schlossmacher, Division of Neurosciences, Ottawa Health Research Institute, University of Ottawa, Canada: Proteins associated with Lewy body disease.

Neuroproteomics:

Prof Tom Gordon and Dr Georgia Arentz, Discipline of Immunology, Allergy & Arthritis, Flinders University: Molecular characterisation of autoimmune antibodies in Sjögren's syndrome by mass spectrometry.

Prof Keryn Williams, Dr Alex Collela, Discipline of Ophthalmology, Flinders University: Heritable influences in an animal model of retinopathy of prematurity.

Assoc Prof Jamie Craig, Dr Shiwani Sharma, Discipline of Ophthalmology, Flinders University: Identification of the molecular basis of congenital cataract formation.

Assoc Prof Simon Koblar, Dr Martin Lewis and Michael Dkujic, Department of Medicine, University of Adelaide: Identification of blood biomarkers for patients experiencing trans ischaemic attacks.

Prof Ian Spark and Dr Chris Delaney, Department of Vascular Surgery, Flinders Medical Centre: The effect of different forms of exercise on the clinical, systemic and local biological responses in intermittent claudication.

Prof Kevin Forsythe and Dr Billy Tao, Department of Paediatrics, Flinders Medical Centre: The treatment of childhood nut allergies using denatured nut therapy.

Oxidative Stress / Neuroprotection:

Prof Peter Blumbergs (Dept of Neuropathology, IMVS Adelaide) and Dr Håkan Muyderman (Medical Biochemistry, Flinders University): The mechanisms of neurodegeneration and cellular antioxidant responses in Parkinson's and Alzheimer's diseases.

Dr Sonja Klebe, Dept of Anatomical Pathology, Flinders Medical Centre: Distribution of antioxidant enzymes in the human eye and their association with eye diseases.

Latest Media Appearances

  • WeiPing Gai - Encounter, Flinders University Alumni Magazine, Tapping into Flinders brain power, p22, Volume 24, 2013-14.

Selected Recent Publications

Majd S, Chegini F, Chataway T, Zhou XF, Gai W (2013) Reciprocal induction between α-synuclein and β-amyloid in adult rat neurons. Neurotoxicity Research, 23(1):69-78

Zhou J, Broe M, Huang Y, Anderson JP, Gai WP, Milward EA, Porritt M, Howells D, Hughes AJ, Wang X, Halliday GM (2011) Changes in the solubility and phosphorylation of alpha-synuclein over the course of Parkinson's disease. Acta Neuropathologica, 121(6):695-704

Pountney DL, Dickson TC, Power JH, Vickers JC, West AJ, Gai WP (2011) Association of metallothionein-III with oligodendroglial cytoplasmic inclusions in multiple system atrophy. Neurotoxicity Research, 19(1):115-22

Wilson A, Carati C, Gannon B, Haberberger R, Chataway T (2010) Aquaporin-1 in rat circumventricular organ blood vessels. Cell and Tissue Research, 340:159-168

Wang YJ, Valadares D, Sun Y, Wang X, Zhong JH, Liu XH, Majd S, Chen L, Gao CY, Chen S, Lim Y, Pollard A, Aguilar E, Gai WP, Yang M, Zhou XF (2010) Effects of proNGF on neuronal viability, neurite growth and amyloid-beta metabolism. Neurotoxicity Research, 17(3):257-67

Seidel K, Schöls L, Nuber S, Petrasch-Parwez E, Gierga K, Wszolek Z, Dickson D, Gai WP, Bornemann A, Riess O, Rami A, Den Dunnen WF, Deller T, Rüb U, Krüger R (2010) First appraisal of brain pathology owing to A30P mutant alpha-synuclein. Annals of Neurology, 67(5):684-9. Erratum in: Annals of Neurology, 67(6):841

Paleologou KE, Oueslati A, Shakked G, Rospigliosi CC, Kim HY, Lamberto GR, Fernandez CO, Schmid A, Chegini F, Gai WP, Chiappe D, Moniatte M, Schneider BL, Aebischer P, Eliezer D, Zweckstetter M, Masliah E, Lashuel HA (2010) Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions. Journal of Neuroscience, 30(9):3184-98

Kragh CL, Lund LB, Febbraro F, Hansen HD, Gai W, El-Agnaf O, Richter-Landsberg C & Jensen P (2009) Alpha-synuclein aggregation and ser-129 phosphorylation-dependent cell death in oligodendroglial cells. Journal of Biological Chemistry, 284(15):10211-10222

Power JH & Blumbergs PC (2009) Cellular glutathione peroxidase in human brain: cellular distribution, and its potential role in the degradation of Lewy bodies in Parkinson's disease and dementia with Lewy bodies. Acta Neuropathologica, 117(1):63-73

Power JHT & Blumbergs PC (2009) Glutathione peroxidase in human brain: cellular distribution and its potential role in the degradation of Lewy bodies in Parkinson's disease and dementia with Lewy bodies. Acta Neuropathologica, 117:63-73

Sharma S, Chataway TK, Burdon KP, Jonavicius L, Klebe S, Hewitt AW, Mills RA & Craig J (2009) Identification of LOXL1 protein and Apolipoprotein E as components of surgically isolated pseudoexfoliation material by direct mass spectrometry. Experimental Eye Research, 89(4):479-485

Lee J, Lee I, Choe Y, Kang S, Kim HY, Gai W, Hahn J & Paik SR (2009) Real-time analysis of amyloid fibril formation of alpha-synuclein using a fibrillation-state-specific fluorescent probe of JC-1. Biochemical Journal, 418(2):311-323

Waldvogel H, Baer K, Gai W, Gilbert R, Rees M, Mohler H, Faull RL (2008) Differential localisation of GABAA receptor subunits within the substantia nigra of the human brain: an immunohistochemical study. Journal of Comparative Neurology, 506:912-929

Pountney DL, Raftery MJ, Chegini F, Blumbergs PC, Gai WP (2008) NSF, Unc-18-1 (rbSEC1), Dynamin-1 and HSP90 are components of nuclear inclusion bodies linked to SUMO-1. Acta Neuropathologica, 116(6):603-14

Kirik D, Gai WP, Jensen PH (2008) Is alpha-synuclein the culprit of the Parkinsonian neurodegeneration? Experimental Neurology, 209:3-4

Huang Y, Song YJ, Murphy K, Holton JL, Lashley T, Revesz T, Gai WP, Halliday GM (2008) LRRK2 and parkin immunoreactivity in multiple system atrophy inclusions. Acta Neuropathologica, 116(6):639-46

Power JHT, Asad SK, Chataway TK, Chegini F, Manavis J, Temlett JA, Jensen PJ, Blumbergs PC, Gai WP (2008) Peroxiredoxin 6 in human brain: molecular forms, cellular distribution and association with Alzheimer's disease pathology. Acta Neuropathologica, 115(6):611-22

Lee JO, Lee IH, Choe YJ, Kang S, Hui Kim HY, Gai WP, Hahn JS, Paik SR (2008) Real-time analysis of amyloid fibril formation of alpha-synuclein with a fibrillation state-specific fluorescent probe of JC-1. Biochemical Journal, 418(2):311-323

 

 

Updated March 17, 2014