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Review of Metabolomics-Based Biomarker Research for Parkinson’s Disease

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Abstract

Parkinson’s disease (PD), as the second most common neurodegenerative disease, is seriously affecting the life quality of the elderly. However, there is still a lack of efficient medical methods to diagnosis PD before apparent symptoms occur. In recent years, clinical biomarkers including genetic, imaging, and tissue markers have exhibited remarkable benefits in assisting PD diagnoses. Due to the advantages of high-throughput detection of metabolites and almost non-invasive sample collection, metabolomics research of PD is widely used for diagnostic biomarker discovery. However, there are also a few shortages for those identified biomarkers, such as the scarcity of verifications regarding the sensitivity and specificity. Thus, reviewing the research progress of PD biomarkers based on metabolomics techniques is of great significance for developing PD diagnosis. To comprehensively clarify the progress of current metabolic biomarker studies in PD, we reviewed 20 research articles regarding the discovery and validation of biomarkers for PD diagnosis from three mainstream academic databases (NIH PubMed, ISI Web of Science, and Elsevier ScienceDirect). By analyzing those materials, we summarized the metabolic biomarkers identified by those metabolomics studies and discussed the potential approaches used for biomarker verifications. In conclusion, this review provides a comprehensive and updated overview of PD metabolomics research in the past two decades and particularly discusses the validation of disease biomarkers. We hope those discussions might provide inspiration for PD biomarker discovery and verification in the future.

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Abbreviations

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

ATP:

Adenosine triphosphate

BCAAs:

Branched chain amino acids

CSF:

Cerebrospinal fluid

CIS:

Clinically isolated syndrome of demyelination

ELISA:

Enzyme-linked immunosorbent assay

FFAs:

Free fatty acids

FMT:

Fecal microbiota transplantation

GBA:

Glucocerebrosidase

GC-MS:

Gas chromatography-mass spectrometry

GST:

Glutathione S-transferase

GSTT1:

Glutathione S-transferase theta 1

GSTM1:

Glutathione S-transferase mu 1

G2019S:

Glycine to serine substitution at amino acid 2019

HD:

Huntington’s disease

iPSC:

Induced pluripotent stem cells

ISI:

Institute for Scientific Information

KA:

Kynurenic acid

KYN:

Kynurenine

LBs:

Lowy bodies

LC-MS:

Liquid chromatography-mass spectrometry

LCECA:

High performance liquid chromatography coupled with electrochemical array detection

L-DOPA:

L-3,4-dihydroxyphenylalanine

LRRK2:

Leucine-rich repeat kinase-2

MDS-UPDRS:

Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale

MND:

Motor neuron disease

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MPP + :

1-Methyl-4-phenylpyridinium cation

MS:

Mass spectrometry

NAA:

N-acetyl aspartate

NDs:

Neurodegenerative diseases

NIH:

National Institutes of Health

NMR:

Nuclear magnetic resonance

PARK2:

Parkin RBR E3 ubiquitin-protein ligase

PD:

Parkinson’s disease

PUFAs:

Polyunsaturated free fatty acids

QA:

Quinolinic acid

SNpc:

Substantia nigra pars compacta

SD rats:

Sprague Dawley rats

TCA:

Tricarboxylic acid

UHPLC-MS:

Ultra high-performance liquid chromatography coupled with mass spectrometry

UHPLC-TOF-MS:

Ultra high-performance liquid chromatography coupled with time-of-flight mass spectrometry

6-OHDA:

6-Hydroxydopamine

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Funding

This study is financially supported by the National Natural Science Foundation of China (81403177), the Innovative Talents Support Program of Liaoning Province (LR2018047), and the Natural Science Foundation of Liaoning Province (2021-MS-150).

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  1. School of Pharmaceutical Sciences, Liaoning University, No. 66 Chongshan Middle Road, Huanggu District, Liaoning Province, 110036, Shenyang, People’s Republic of China

    Xin Li, Xiaoying Fan, Hongtian Yang & Yufeng Liu

  2. Natural Products Pharmaceutical Engineering Technology Research Center of Liaoning Province, Shenyang, 110036, People’s Republic of China

    Yufeng Liu

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  1. Xin Li
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  2. Xiaoying Fan
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  3. Hongtian Yang
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  4. Yufeng Liu
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All authors contributed to the study conception and design. Literature collection and analysis were performed by Xin Li, Xiaoying Fan, and Hongtian Yang. The manuscript was written by Xin Li and proved by Xin Li, Xiaoying Fan, Hongtian Yang and Yufeng Liu. All authors reviewed and approved the final manuscript.

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Li, X., Fan, X., Yang, H. et al. Review of Metabolomics-Based Biomarker Research for Parkinson’s Disease. Mol Neurobiol 59, 1041–1057 (2022). https://doi.org/10.1007/s12035-021-02657-7

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