Cappai laboratory: Neurodegeneration and Brain Injury

Researcher

Research Overview

The major research interests of my group is focused on the key neurological disorders of Alzheimer's Disease, Parkinson's Disease, Motor Neuron Disease, Stroke and Traumatic Brain Injury. The group is studying the key proteins associated with these diseases with a major focus on the Amyloid Precursor Protein (APP) family, Amyloid-beta peptide and alpha-synuclein. We want to identify the critical molecular interactions and cellular pathways that cause the neuronal dysfunction / death that underpin these diseases, and to develop therapeutic approaches based on targeting these proteins and pathways. We have a strong interest in metallobiology, protein aggregation, protein-protein interactions, protein structure, neuroprotection, neuronal differentiation and neurodegeneration.

The lab utilises molecular biology, cell biology (primary cells and immortalized cell lines), animal models of disease, recombinant protein expression and purification, gene expression analysis and protein chemistry.

Objectives

  • To determine the function of the Amyloid Precursor Protein family in modulating traumatic brain injury and motor neurone disease
  • To determine the key molecular interactions and cellular pathways that are critical for modulating protein aggregation and neurotoxicity in Alzheimer's and Parkinson's disease.

Major Achievements

  • Identifying APP as a neuroprotective modulator of traumatic brain injury
  • Solving the structure of key domains of the APP-family.
  • Identifying APP as a modulator of metal homeostasis.
  • Identifying dopamine as a modulator of α-synuclein aggregation.

Staff

Ms Chaitanya Inampudi - PhD Student
Ms Phan Truong
- PhD Student
Ms Marsha Tan - PhD Student

Collaborators

Departmental

Associate Professor Peter Crack - Neuropharmacology Lab
Associate Professor Peter Crouch - Neurodegenerative Diseases Lab
Associate Professor Tony Velkov - Anti-infective Pharmacology Lab

University

Dr Blaine Roberts - The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia

External

National Collaborators
Associate Professor Corinna van den Heuvel - The University of Adelaide, Australia
Dr Frances Corrigan - University of South Australia, Australia

International Collaborators
Professor Gerd Multhaup, Dr Lisa-Marie Munter - McGill University, Montreal, Canada
Professor Sasanka Chakrabarti - IIMSAR, Haldia, India
Dr Frédéric Mascarelli - INSERM, Centre de Recherche des Cordeliers, Paris, France

Funding

  • NHMRC

Research Publications

See a full list of Professor Roberto Cappai's publications on PubMed.

  1. Luu L, Ciccotosto GD, Vella LJ, Cheng L, Roisman LC, Multhaup G, Hill AF, Munter LM, Cappai R. Amyloid Precursor Protein Dimerisation Reduces Neurite Outgrowth. Mol Neurobiol. 2018 Apr 19. doi: 10.1007/s12035-018-1070-4.
  2. Plummer SL, Corrigan F, Thornton E, Woenig JA, Vink R, Cappai R, Van Den Heuvel C. The amyloid precursor protein derivative, APP96-110, is efficacious following intravenous administration after traumatic brain injury. PLoS One. 2018 Jan 10;13(1):e0190449. doi: 10.1371/journal.pone.0190449.
  3. Dinet V, Ciccotosto GD, Delaunay K, Borras C, Ranchon-Cole I, Kostic C, Savoldelli M, El Sanharawi M, Jonet L, Pirou C, An N, Abitbol M, Arsenijevic Y, Behar-Cohen F, Cappai R, Mascarelli F.  Amyloid Precursor-Like Protein 2 deletion-induced retinal synaptopathy related to congenital stationary night blindness: structural, functional and molecular characteristics. Mol Brain. 2016 Jun 8;9(1):64. doi: 10.1186/s13041-016-0245-z.
  4. Jana MK, Cappai R, Ciccotosto GD. Oligomeric Amyloid-β Toxicity Can Be Inhibited by Blocking Its Cellular Binding in Cortical Neuronal Cultures with Addition of the Triphenylmethane Dye Brilliant Blue G. ACS Chem Neurosci. 2016 Aug 17;7(8):1141-7. doi: 10.1021/acschemneuro.6b00108.
  5. Jana MK, Cappai R, Pham CL, Ciccotosto GD.  Membrane-bound tetramer and trimer Aβ oligomeric species correlate with toxicity towards cultured neurons. J Neurochem. 2016 Feb;136(3):594-608. doi: 10.1111/jnc.13443
  6. Leong SL, Hinds MG, Connor AR, Smith DP, Illes-Toth E, Pham CL, Barnham KJ, Cappai R.The N-terminal residues 43 to 60 form the interface for dopamine mediated α-synuclein dimerisation. PLoS One. 2015 Feb 13;10(2):e0116497. doi: 10.1371/journal.pone.0116497
  7. Bir A, Sen O, Anand S, Khemka VK, Banerjee P, Cappai R, Sahoo A, Chakrabarti S. α-Synuclein-induced mitochondrial dysfunction in isolated preparation and intact cells: implications in the pathogenesis of Parkinson's disease. J Neurochem. 2014 Dec;131(6):868-77. doi: 10.1111/jnc.12966.
  8. Vella LJ, Cappai R.  Identification of a novel amyloid precursor protein processing pathway that generates secreted N-terminal fragments. FASEB J 2012; 26(7): 2930-40. doi: 10.1096/fj.11-200295

Research Projects

This Research Group doesn't currently have any projects



Faculty Research Themes

Neuroscience

School Research Themes

Biomedical Neuroscience, Molecular Mechanisms of Disease



Key Contact

For further information about this research, please contact Head of Laboratory Professor Roberto Cappai

Department / Centre

Pharmacology and Therapeutics

Unit / Centre

Cappai laboratory: Neurodegeneration and Brain Injury


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