Metabolic Biomarkers and Neurodegeneration: A Pathway Enrichment Analysis of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis.
Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) lack robust diagnostics and prognostic biomarkers. Metabolomics is a postgenomics field that offers fresh insights for biomarkers of common complex as well as rare diseases. Using data on metabolite-disease associations published in the previous decade (2006-2016) in PubMed, ScienceDirect, Scopus, and Web of Science, we identified 101 metabolites as putative biomarkers for these three neurodegenerative diseases. Notably, uric acid, choline, creatine, L-glutamine, alanine, creatinine, and N-acetyl-L-aspartate were the shared metabolite signatures among the three diseases. The disease-metabolite-pathway associations pointed out the importance of membrane transport (through ATP binding cassette transporters), particularly of arginine and proline amino acids in all three neurodegenerative diseases. When disease-specific and common metabolic pathways were queried by using the pathway enrichment analyses, we found that alanine, aspartate, glutamate, and purine metabolism might act as alternative pathways to overcome inadequate glucose supply and energy crisis in neurodegeneration. These observations underscore the importance of metabolite-based biomarker research in deciphering the elusive pathophysiology of neurodegenerative diseases. Future research investments in metabolomics of complex diseases might provide new insights on AD, PD, and ALS that continue to place a significant burden on global health.
Department of Bioengineering, Faculty of Engineering, Marmara University , Istanbul, Turkey .
Medi
M
Kori
Department of Bioengineering, Faculty of Engineering, Marmara University , Istanbul, Turkey .
Busra
B
Aydın
Department of Bioengineering, Faculty of Engineering, Marmara University , Istanbul, Turkey .
Semra
S
Unal
Department of Bioengineering, Faculty of Engineering, Marmara University , Istanbul, Turkey .
Kazim Yalcin
KY
Arga
Department of Bioengineering, Faculty of Engineering, Marmara University , Istanbul, Turkey .
Dilek
D
Kazan
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001826:Body Fluids / Q000378:metabolism; D019295:Computational Biology; D006801:Humans; D050356:Lipid Metabolism; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D010300:Parkinson Disease / Q000378:metabolism*; D011379:Prognosis
D018528:ATP-Binding Cassette Transporters; D000596:Amino Acids; D015415:Biomarkers
bioinformatics; biomarkers; metabolomics; neurodegeneration; systems biology