Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Oct 23;25(21):11406.
doi: 10.3390/ijms252111406.

Integrative Metabolome and Proteome Analysis of Cerebrospinal Fluid in Parkinson's Disease

Seok Gi Kim  1   2 , Ji Su Hwang  1   2 , Nimisha Pradeep George  1   2 , Yong Eun Jang  1   2 , Minjun Kwon  1   2 , Sang Seop Lee  3 , Gwang Lee  1   2
Affiliations
Review

Integrative Metabolome and Proteome Analysis of Cerebrospinal Fluid in Parkinson's Disease

Seok Gi Kim et al. Int J Mol Sci. .

Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Recent studies have highlighted the significant role of cerebrospinal fluid (CSF) in reflecting pathophysiological PD brain conditions by analyzing the components of CSF. Based on the published literature, we created a single network with altered metabolites in the CSF of patients with PD. We analyzed biological functions related to the transmembrane of mitochondria, respiration of mitochondria, neurodegeneration, and PD using a bioinformatics tool. As the proteome reflects phenotypes, we collected proteome data based on published papers, and the biological function of the single network showed similarities with that of the metabolomic network. Then, we analyzed the single network of integrated metabolome and proteome. In silico predictions based on the single network with integrated metabolomics and proteomics showed that neurodegeneration and PD were predicted to be activated. In contrast, mitochondrial transmembrane activity and respiration were predicted to be suppressed in the CSF of patients with PD. This review underscores the importance of integrated omics analyses in deciphering PD's complex biochemical networks underlying neurodegeneration.

Keywords: Parkinson’s disease; cerebrospinal fluid; integrated omics; metabolomics; proteomics.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Biological functions and disease-related metabolomic network from ingenuity pathway analysis (IPA). (A) Network of metabolites and associated functions and diseases in the cerebrospinal fluid of patients with Parkinson’s disease. (B) Prediction of the metabolomic network through the altered level of metabolites. Red and green indicate increased and decreased metabolites in the CSF of PD patients, respectively. Orange and blue represent the activation and inhibition of metabolites, functions, and diseases. Solid and dotted line represents direct and indirect relationships, respectively.
Figure 2
Figure 2
Biological functions and disease-related proteomic network from ingenuity pathway analysis (IPA). (A) Network of proteins and associated functions and diseases in the cerebrospinal fluid of patients with Parkinson’s disease. (B) Prediction of the proteomic network through the altered level of proteins. Increased levels of proteins are represented in red, while decreased levels are represented in green. Blue indicates the predicted inhibition, and orange shows the expected activation of cellular functions or diseases. Solid and dotted line represents direct and indirect relationships, respectively.
Figure 3
Figure 3
Integrative omics network prediction and omics analyses from ingenuity pathway analysis (IPA). (A) Integrative omics network with metabolome and proteome. (B) Prediction of the integrative omics network with cellular functions and diseases. Red and green indicate increased and decreased molecules in the CSF of PD patients, respectively. Orange and blue represent the activation and inhibition of molecules, functions, and diseases. Solid and dotted line represents direct and indirect relationships, respectively. (C,D) Integrative omics analyses of the top seven activated/inhibited canonical pathways (C) and diseases and biological functions (D). A negative or positive activation z-score indicates inhibition or activation, respectively. VEC: vascular endothelial cell.
See this image and copyright information in PMC

References

    1. Thomas B., Beal M.F. Parkinson’s disease. Hum. Mol. Genet. 2007;16:R183–R194. doi: 10.1093/hmg/ddm159. - DOI - PubMed
    1. Bayati A., McPherson P.S. alpha-synuclein, autophagy-lysosomal pathway, and Lewy bodies: Mutations, propagation, aggregation, and the formation of inclusions. J. Biol. Chem. 2024;300:107742. doi: 10.1016/j.jbc.2024.107742. - DOI - PMC - PubMed
    1. Poewe W. Non-motor symptoms in Parkinson’s disease. Eur. J. Neurol. 2008;15((Suppl. 1)):14–20. doi: 10.1111/j.1468-1331.2008.02056.x. - DOI - PubMed
    1. Leite Silva A.B.R., Goncalves de Oliveira R.W., Diogenes G.P., de Castro Aguiar M.F., Sallem C.C., Lima M.P.P., de Albuquerque Filho L.B., Peixoto de Medeiros S.D., Penido de Mendonca L.L., de Santiago Filho P.C., et al. Premotor, nonmotor and motor symptoms of Parkinson’s Disease: A new clinical state of the art. Ageing Res. Rev. 2023;84:101834. doi: 10.1016/j.arr.2022.101834. - DOI - PubMed
    1. Bose A., Beal M.F. Mitochondrial dysfunction in Parkinson’s disease. J. Neurochem. 2016;139((Suppl. 1)):216–231. doi: 10.1111/jnc.13731. - DOI - PubMed