Proteomics in Human Parkinson’s Disease: Present Scenario and Future Directions

Abstract

Parkinson’s disease (PD) is an age-related, threatening neurodegenerative disorder with no reliable treatment till date. Identification of specific and reliable biomarker is a major challenge for disease diagnosis and designing effective therapeutic strategy against it. PD pathology at molecular level involves abnormal expression and function of several proteins, including alpha-synuclein. These proteins affect the normal functioning of neurons through various post-translational modifications and interaction with other cellular components. The role of protein anomalies during PD pathogenesis can be better understood by the application of proteomics approach. A number of proteomic studies conducted on brain tissue, blood, and cerebrospinal fluid of PD patients have identified a wide array of protein alterations underlying disease pathogenesis. However, these studies are limited by the types of brain regions or biofluids utilized in the research. For a complete understanding of PD mechanism and discovery of reliable protein biomarkers, it is essential to analyze the proteome of different PD-associated brain regions and easily accessible biofluids such as saliva and urine. The present review summarizes the major advances in the field of PD research in humans utilizing proteomic techniques. Moreover, potential samples for proteomic analysis and limitations associated with the analyses of different types of samples have also been discussed.

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Fig. 1

Abbreviations

PD:

Parkinson’s disease

UCHL1:

Ubiquitin carboxy-terminal hydrolase L1

LRRK2:

Leucine-rich repeat kinase 2

PINK1:

PTEN-induced kinase 1

LNs:

Lewy neurites

LBs:

Lewy bodies

LC:

Locus coeruleus

SN:

Substantia nigra

Prx:

Peroxiredoxin

CSF:

Cerebrospinal fluid

GGH:

Gamma glutamyl hydrolase

SOD:

Superoxide dismutase

AD:

Alzheimer’s disease

Apo:

Apolipoprotein

TIMP1:

Metalloproteinase inhibitor 1

APLP1:

Amyloid-like protein 1

LRP1:

Prolow-density lipoprotein receptor-related protein 1

CSF1R:

Macrophage colony-stimulating factor 1 receptor

EPHA4:

Ephrin type-A receptor 4

PRNP:

Major prion protein

HSPG2:

Heparan sulfate proteoglycan 2

MEGF8:

Multiple EGF-like domains 8

NCAM1:

Neural cell adhesion molecule 1

2-DE:

Two-dimensional gel electrophoresis

2-D DIGE:

Two-dimensional difference gel electrophoresis

MALDI-TOF/TOF-MS:

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

MALDI-IMS:

MALDI imaging mass spectrometry

LC-ESI-MS/MS:

Liquid chromatography-electrospray ionization tandem mass spectrometry

ESI-Q-TOF MS/MS:

Electrospray-quadrupole-time-of-flight tandem mass spectrometry

ESI-MS:

Electrospray ionization mass spectrometry

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Acknowledgements

Dr. M. P. Singh and CSIR-Indian Institute of Toxicology Research, Lucknow, India are acknowledged for providing guidance and research facilities to AD.

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AD-Review design, literature collection, data interpretation, and manuscript preparation. RM-Review design and manuscript preparation. AKS-Review design and manuscript preparation.

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Correspondence to Anubhuti Dixit.

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Dixit, A., Mehta, R. & Singh, A.K. Proteomics in Human Parkinson’s Disease: Present Scenario and Future Directions. Cell Mol Neurobiol 39, 901–915 (2019). https://doi.org/10.1007/s10571-019-00700-9

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Keywords

  • Biomarker
  • Human
  • Parkinson’s disease
  • Proteomics