Abstract | BACKGROUND: RESULTS: Here we establish a screening assay and criteria to identify post-mortem brain samples containing well-preserved synapse proteomes, revealing that neocortex samples are best preserved. We also develop a rapid method for the isolation of synapse proteomes from human brain, allowing large numbers of post-mortem samples to be processed in a short time frame. We perform the first purification and proteomic mass spectrometry analysis of MAGUK Associated Signalling Complexes (MASC) from neurosurgical and post-mortem tissue and find genetic evidence for their involvement in over seventy human brain diseases. CONCLUSIONS: We have demonstrated that synaptic proteome integrity can be rapidly assessed from human post-mortem brain samples prior to its analysis with sophisticated proteomic methods. We have also shown that proteomics of synapse multiprotein complexes from well preserved post-mortem tissue is possible, obtaining structures highly similar to those isolated from biopsy tissue. Finally we have shown that MASC from human synapses are involved with over seventy brain disorders. These findings should have wide application in understanding the synaptic basis of psychiatric and other mental disorders.
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Authors | Àlex Bayés, Mark O Collins, Clare M Galtrey, Clémence Simonnet, Marcia Roy, Mike D R Croning, Gemma Gou, Louie N van de Lagemaat, David Milward, Ian R Whittle, Colin Smith, Jyoti S Choudhary, Seth G N Grant |
Journal | Molecular brain
(Mol Brain)
Vol. 7
Pg. 88
(Nov 28 2014)
ISSN: 1756-6606 [Electronic] England |
PMID | 25429717
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Membrane Proteins
- Nerve Tissue Proteins
- Proteome
- postsynaptic density proteins
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Topics |
- Cerebral Cortex
(metabolism)
- Chromatography, Affinity
- Humans
- Membrane Proteins
(metabolism)
- Nerve Tissue Proteins
(metabolism)
- Postmortem Changes
- Proteome
(metabolism)
- Proteomics
- Signal Transduction
- Subcellular Fractions
(metabolism)
- Synapses
(metabolism)
- Tissue Banks
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