2018
DOI: 10.1051/ocl/2018027
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Small molecule biomarkers in Alzheimer’s disease

Abstract: -Alzheimer's disease (AD) is a progressive neurodegenerative disease which affects a growing number of people as the population ages worldwide. Alzheimer's Disease International estimated that more than 100 million people will be living with dementia by 2050. At present there are no disease-modifying therapies and research has expanded to the Àomic sciences with scientists aiming to get a holistic view of the disease using systems medicine. Metabolomics and Lipidomics give a snap-shot of the metabolism. As ana… Show more

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Cited by 6 publications
(8 citation statements)
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References 212 publications
(221 reference statements)
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“…Interestingly, both plasma and CSF metabolomics comparison of patients with Alzheimer’s disease (AD) to matched cognitive healthy controls identified a similar increase of several citrate cycle intermediates such as citrate, aconitate, and α-ketoglutarate in AD 53 , 54 . Importantly, there is a well characterized reduction in activity of the rate limiting citrate cycle enzyme α-ketoglutarate dehydrogenase which converts α-ketoglutarate to succinyl-CoA 55 , 56 that may be a key event in AD pathogenesis as well as various other neurodegenerative diseases due to oxidative stress 54 . Reduced α-ketoglutarate dehydrogenase may result in accumulation of α-ketoglutarate.…”
Section: Discussionmentioning
confidence: 99%
“…Interestingly, both plasma and CSF metabolomics comparison of patients with Alzheimer’s disease (AD) to matched cognitive healthy controls identified a similar increase of several citrate cycle intermediates such as citrate, aconitate, and α-ketoglutarate in AD 53 , 54 . Importantly, there is a well characterized reduction in activity of the rate limiting citrate cycle enzyme α-ketoglutarate dehydrogenase which converts α-ketoglutarate to succinyl-CoA 55 , 56 that may be a key event in AD pathogenesis as well as various other neurodegenerative diseases due to oxidative stress 54 . Reduced α-ketoglutarate dehydrogenase may result in accumulation of α-ketoglutarate.…”
Section: Discussionmentioning
confidence: 99%
“…In AD for example, the recent FDA approval of antibodies 13 targeting Ab peptide aggregation has renewed interest in the development of small-molecule agents that target this pathway. 14 In cancer, there is significant interest in the development of small molecules capable of reactivating mutant p53 protein in cancer. The p53 protein is commonly regarded as 'the guardian of the genome' and is responsible for regulating critical processes such as apoptosis, DNA repair, and cell cycle arrest of damaged cells.…”
Section: Grace Leechmentioning
confidence: 99%
“…APP transgenic mouse, a well-established AD animal model, was widely used to study the metabolomic changes related to AD [38]. A significant increase of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin, has been reported in the urine of AD model mice [39].…”
Section: Metabolitesmentioning
confidence: 99%