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Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

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Abstract

Brain extracellular matrix (ECM) is a highly organized system that consists of collagens, noncollagenous proteins, glycoproteins, hyaluronan, and proteoglycans. Recognized physiological roles of ECM include developmental regulation, tissue homeostasis, cell migration, cell proliferation, cell differentiation, neuronal plasticity, and neurite outgrowth. Aberrant ECM structure is associated with brain neurodegenerative conditions. This review focuses on two neurodegenerative conditions, schizophrenia and Alzheimer’s disease, and summarizes recent findings of altered ECM components, including proteoglycans, glycosaminoglycans, proteins, and glycoproteins, and proteins and genes related to other brain components. The scope includes immunohistochemical, genomics, transcriptomics, proteomics, and glycomics studies, and a critical assessment of current state of proteomic studies for neurodegenerative disorders. The intent is to summarize the ECM molecular alterations associated with neurodegenerative pathophysiology.

Brain extracellular matrix showing HSPGs, CSPGs, HA, collagens, and other glycoproteins.

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Abbreviations

Aβ:

Amyloid beta

AD:

Alzheimer’s disease

ADAM:

A disintegrin and metalloprotease

ADAMTS:

A disintegrin and metalloprotease with thrombospondin motifs

APP:

Amyloid beta A4 precursor protein

BACE1:

β-site amyloid beta A4 precursor protein cleaving enzyme 1

CS:

Chondroitin sulfate

CSF:

Cerebrospinal fluid

CSPG:

Chondroitin sulfate proteoglycan

DS:

Dermatan sulfate

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

GAG:

Glycosaminoglycan

GalNAc:

N-acetylgalactosamine

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

GlcNAc:

N-acetylglucosamine

GlcNAcT:

N-acetylglucosamine transferase

HA:

Hyaluronan

HS:

Heparan sulfate

HSPG:

Heparan sulfate proteoglycan

KS:

Keratan sulfate

LC:

Liquid chromatography

MMP:

Matrix metalloprotease

MS/MS:

Tandem mass spectrometry

PFC:

Prefrontal cortex

PG:

Proteoglycan

PNN:

Perineuronal net

PTM:

Post-translational modification

RPTPβ:

Receptor phosphotyrosine phosphatase beta/zeta

SZ:

Schizophrenia

WFA:

Wisteria floribunda agglutinin

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Acknowledgments

This work was supported by NIH grants P41GM104602, R21CA177479, and R01MH105608.

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  1. Center for Biomedical Mass Spectrometry, Department of Biochemistry, Cell Biology & Genomics, Boston University School of Medicine, Boston, MA, 02118, USA

    Manveen K. Sethi & Joseph Zaia

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Published in the topical collection Glycomics Glycoproteomics and Allied Topics with guest editors Yehia Mechref and David Muddiman.

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Sethi, M.K., Zaia, J. Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease. Anal Bioanal Chem 409, 379–394 (2017). https://doi.org/10.1007/s00216-016-9900-6

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