Journal article

An Atlas of Phosphorylation and Proteolytic Processing Events During Excitotoxic Neuronal Death Reveals New Therapeutic Opportunities

S Sadia Ameen, Antoine Dufour, M Iqbal Hossain, Ashfaqul Hoque, Sharelle Sturgeon, Harshal Nandurkar, Dominik Draxler, Robert Medcalf, Mohd Aizuddin Kamaruddin, Isabelle S Lucet, Michael G Leeming, Dazhi Liu, Amardeep Dhillon, Jet Phey Lim, Hong-Jian Zhu, Laita Bokhari, Carli Roulston, Oded Kleifeld, D Ciccotosto Giuseppe, Nicholas A Williamson Show all

Cold Spring Harbor Laboratory

Abstract

SummaryExcitotoxicity, a neuronal death process in neurological disorders, is initiated by over-stimulation of neuronal ionotropic glutamate receptors. The over-stimulated receptors dysregulate proteases, protein kinases and phosphatases, which in turn modify target neuronal proteins to induce cell death. To decipher this cell death mechanism, we used quantitative proteomics, phosphoproteomics and N-terminomics to identify modified proteins in excitotoxic neurons. Data, available in ProteomeXchange (identifiers: PXD019527 and PXD019211), enabled us to identify over one thousand such proteins with calpains, cathepsins and over twenty protein kinases as their major modifiers. These protein mod..

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