Poster Presentation 23rd Annual Lorne Proteomics Symposium 2018

Non-protein amino acids and neurological disease: their detection in human proteins and effects (#139)

Joel R Steele 1 , Kenneth J Rodgers 1 , Matthew P Padula 1
  1. University of Technology Sydney, Ultimo, NSW, Australia

Neurological diseases are hallmarked by protein aggregation and neuronal apoptosis in major diseases such as; Parkinson’s; Alzheimer’s and Motor Neurone disease. In 90% of disease cases there is no underlying genetic abnormality that defines pathogenesis. Certain non-protein amino acids (NPAAs) have been presented by the literature to be a possible causative agent in these sporadic cases, such as the NPAA beta-methyl-L-alanine (BMAA) 1 or the therapeutic drug used in Parkinson’s disease (Levodopa) 2. The mechanism underlying these NPAAs is hypothesised to be miss-incorporated into proteins in place of protein amino acids, modifying native-protein structures causing misfolded proteins resulting in neuronal aggregates and apoptosis. This was investigated by the use of neuronal neuroblastoma cells (SH-SY5Y) utilising label free and Tandem Mass Tag (TMT) labelling approaches with the use of high resolution mass spectrometry, both data-dependent and independent approaches combined with; exclusion list generation to delve beyond the dynamic limit of detection. This is novel due to protein hydrolysis and amino acid assays being used to infer incorporation in the analytical fields of toxicology to date. These data generated provides proof of NPAA incorporation by use of novel positive controls and spectral evidence including; spectral library generation. These data also provide workflow for the incorporation of NPAAs in clinical samples.


  1. 1:Cox, P. A., D. A. Davis, D. C. Mash, J. S. Metcalf and S. A. Banack (2016). "Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain." Proceedings of the Royal Society B: Biological Sciences 283(1823).
  2. 2:Chan, S.W., Dunlop, R.A., Rowe, A., Double, K.L. and Rodgers, K.J., 2012. L-DOPA is incorporated into brain proteins of patients treated for Parkinson's disease, inducing toxicity in human neuroblastoma cells in vitro. Experimental neurology, 238(1), pp.29-37.