Glycoproteomics in neurodegenerative diseases.
Protein glycosylation regulates protein function and cellular distribution. Additionally, aberrant protein glycosylations have been recognized to play major roles in human disorders, including neurodegenerative diseases. Glycoproteomics, a branch of proteomics that catalogs and quantifies glycoproteins, provides a powerful means to systematically profile the glycopeptides or glycoproteins of a complex mixture that are highly enriched in body fluids, and therefore, carry great potential to be diagnostic and/or prognostic markers. Application of this mass spectrometry-based technology to the study of neurodegenerative disorders (e.g., Alzheimer's disease and Parkinson's disease) is relatively new, and is expected to provide insight into the biochemical pathogenesis of neurodegeneration, as well as biomarker discovery. In this review, we have summarized the current understanding of glycoproteins in biology and neurodegenerative disease, and have discussed existing proteomic technologies that are utilized to characterize glycoproteins. Some of the ongoing studies, where glycoproteins isolated from cerebrospinal fluid and human brain are being characterized in Parkinson's disease at different stages versus controls, are presented, along with future applications of targeted validation of brain specific glycoproteins in body fluids.
Department of Pathology, University of Washington, Seattle, WA 98104, USA.
Hyejin
H
Hwang
Jianpeng
J
Zhang
Kathryn A
KA
Chung
James B
JB
Leverenz
Cyrus P
CP
Zabetian
Elaine R
ER
Peskind
Joseph
J
Jankovic
Zhen
Z
Su
Aneeka M
AM
Hancock
Catherine
C
Pan
Thomas J
TJ
Montine
Sheng
S
Pan
John
J
Nutt
Roger
R
Albin
Marla
M
Gearing
Richard P
RP
Beyer
Min
M
Shi
Jing
J
Zhang
D000595:Amino Acid Sequence; D006023:Glycoproteins / Q000032:analysis* / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods* / Q000639:trends; D008969:Molecular Sequence Data; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000378:metabolism*; D040901:Proteomics / Q000379:methods* / Q000639:trends
D006023:Glycoproteins