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Human post-mortem synapse proteome integrity screening for proteomic studies of postsynaptic complexes.

Àlex Bayés, Mark O Collins, Clare M Galtrey

    Molecular Brain
    |November 29, 2014
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    Researchers developed a method to analyze synapse protein complexes from post-mortem brain tissue, revealing their link to over seventy brain disorders, including schizophrenia and autism.

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    Area of Science:

    • Neuroscience
    • Proteomics
    • Genetics

    Background:

    • Synapses are crucial for brain function and are implicated in over 100 neurological and psychiatric disorders.
    • Mutations in genes affecting postsynaptic complexes are linked to conditions like schizophrenia, autism, and intellectual disability.
    • Direct analysis of human synapse multiprotein complexes from post-mortem tissue is essential for understanding disease mechanisms but has not been achieved.

    Purpose of the Study:

    • To develop and validate methods for assessing synapse proteome integrity in post-mortem human brain samples.
    • To establish a protocol for the rapid isolation and proteomic analysis of synapse multiprotein complexes from post-mortem tissue.
    • To investigate the role of MAGUK Associated Signalling Complexes (MASC) in human brain diseases.

    Main Methods:

    • Developed a screening assay to identify well-preserved post-mortem brain samples, prioritizing neocortex.
    • Established a rapid isolation technique for synapse proteomes from human brain tissue.
    • Performed proteomic mass spectrometry on isolated MAGUK Associated Signalling Complexes (MASC) from both neurosurgical and post-mortem samples.

    Main Results:

    • Identified neocortex as the brain region with the best-preserved synapse proteomes in post-mortem samples.
    • Successfully isolated and analyzed MASC from human post-mortem tissue, yielding structures comparable to those from biopsy samples.
    • Found genetic evidence linking MASC to over seventy human brain diseases.

    Conclusions:

    • Synaptic proteome integrity in post-mortem human brain samples can be rapidly assessed before proteomic analysis.
    • Proteomic analysis of synapse multiprotein complexes from well-preserved post-mortem tissue is feasible and yields high-quality structural data.
    • MASC isolated from human synapses are implicated in a wide range of over seventy brain disorders, offering insights into synaptic dysfunction in mental illness.