Traditional Food Items in Ogimi, Okinawa: l-Serine Content and the Potential for Neuroprotection

Cox, Paul Alan; Metcalf, James S.

doi:10.1007/s13668-017-0191-0

Cited by 28 publications

(11 citation statements)

References 44 publications

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“…Although it is possible that increasing D-serine concentrations in AD patients may exacerbate glutamate excitotoxicity, this would probably not occur at an early stage of the pathology, when memantine is not yet effective (Schneider et al, 2011). It is noteworthy that people living in Okinawa, a Japanese island known for the overall longevity of its population, have a diet characterized by an L-serine content that is four times higher than that of the average American (Cox and Metcalf, 2017).…”

Section: Discussionmentioning

confidence: 99%

Impairment of Glycolysis-Derived l-Serine Production in Astrocytes Contributes to Cognitive Deficits in Alzheimer’s Disease

et al. 2020

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Alteration of brain aerobic glycolysis is often observed early in the course of Alzheimer's disease (AD). Whether and how such metabolic dysregulation contributes to both synaptic plasticity and behavioral deficits in AD is not known. Here, we show that the astrocytic L-serine biosynthesis pathway, which branches from glycolysis, is impaired in young AD mice and in AD patients. L-serine is the precursor of D-serine, a co-agonist of synaptic NMDA receptors (NMDARs) required for synaptic plasticity. Accordingly, AD mice display a lower occupancy of the NMDAR co-agonist site as well as synaptic and behavioral deficits. Similar deficits are observed following inactivation of the L-serine synthetic pathway in hippocampal astrocytes, supporting the key role of astrocytic L-serine. Supplementation with L-serine in the diet prevents both synaptic and behavioral deficits in 3xTg-AD mice. Our findings reveal that astrocytic glycolysis controls cognitive functions and suggest oral L-serine as a ready-to-use therapy for AD.

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Section: Discussionmentioning

confidence: 99%

Impairment of Glycolysis-Derived l-Serine Production in Astrocytes Contributes to Cognitive Deficits in Alzheimer’s Disease

et al. 2020

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“…Certain diets allow for the regular consumption of phytoestrogens, which are readily abundant in the Mediterranean and Okinawan diets, both of which have been linked to improved cognition [14,15,16,17]. Phytoestrogens are also found in many foods in the Western diet but are not as abundant because of the vast differences in dietary patterns and food choices [18].…”

Section: Introductionmentioning

confidence: 99%

Gender Differences in Phytoestrogens and the Relationship with Speed of Processing in Older Adults: A Cross-Sectional Analysis of NHANES, 1999–2002

2019

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Sex hormone changes in adults are known to play a part in aging, including cognitive aging. Dietary intake of phytoestrogens can mimic estrogenic effects on brain function. Since sex hormones differ between genders, it is important to examine gender differences in the phytoestrogen–cognition association. Therefore, the goal of this study is to examine the relationship between urinary phytoestrogens and speed of processing (SOP) and the variation of the association between genders in older adults. Participants were drawn from the 1999–2002 National Health and Nutrition Examination Survey and included 354 individuals aged 65–85 years old. General linear models (GLMs) were used to test for significant gender differences in the relationship between phytoestrogens and SOP. Results from the GLMs showed significant gender differences in the relationship between genistein and SOP. Higher levels of genistein were associated with better SOP in women. This relationship was reversed in men: higher genistein levels were associated with worse performance. Results indicate that there are distinct gender differences in the relationship between genistein and SOP. These results emphasize the importance of considering gender differences when devising dietary and pharmacologic interventions that target phytoestrogens to improve brain health.

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“…Because our study was performed in healthy subjects with no infectious condition, the turnover model or other empirical polynomial models were not considered. Although food intake can affect the circulating levels of amino acids (Bier, 2003), the baseline levels of AST-001 showed a relatively constant value over 24 h. As de novo synthesis (6 g/day) is 2.4 fold higher than the average daily intake from food (2.53 g/day), diet may have a low impact on baseline AST-001 levels (Cox and Metcalf, 2017;Neis et al, 2017). In addition, we restricted the diet to minimize the possible influence of meals during the study.…”

Section: Discussionmentioning

confidence: 92%

Population Pharmacokinetic Model of AST-001, L-Isomer of Serine, Combining Endogenous Production and Exogenous Administration in Healthy Subjects

Lee

Hwang

Nam³

et al. 2022

Front. Pharmacol.

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AST-001 is an L-isomer of serine that has protective effects on neurological disorders. This study aimed to establish a population pharmacokinetic (PK) model of AST-001 in healthy Korean to further propose a fixed-dose regimen in pediatrics. The model was constructed using 648 plasma concentrations from 24 healthy subjects, including baseline endogenous levels during 24 h and concentrations after a single dose of 10, 20, and 30 g of AST-001. For the simulation, an empirical allometric power model was applied to the apparent clearance and volume of distribution with body weight. The PK characteristics of AST-001 after oral administration were well described by a two-compartment model with zero-order absorption and linear elimination. The endogenous production of AST-001 was well explained by continuous zero-order production at a rate of 0.287 g/h. The simulation results suggested that 2 g, 4 g, 7 g, 10 g, and 14 g twice-daily regimens for the respective groups of 10–14 kg, 15–24 kg, 25–37 kg, 38–51 kg, 52–60 kg were adequate to achieve sufficient exposure to AST-001. The current population PK model well described both observed endogenous production and exogenous administration of AST-001 in healthy subjects. Using the allometric scaling approach, we suggested an optimal fixed-dose regimen with five weight ranges in pediatrics for the upcoming phase 2 trial.

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Traditional Food Items in Ogimi, Okinawa: l-Serine Content and the Potential for Neuroprotection

Cited by 28 publications

References 44 publications

Impairment of Glycolysis-Derived l-Serine Production in Astrocytes Contributes to Cognitive Deficits in Alzheimer’s Disease

Impairment of Glycolysis-Derived l-Serine Production in Astrocytes Contributes to Cognitive Deficits in Alzheimer’s Disease

Gender Differences in Phytoestrogens and the Relationship with Speed of Processing in Older Adults: A Cross-Sectional Analysis of NHANES, 1999–2002

Population Pharmacokinetic Model of AST-001, L-Isomer of Serine, Combining Endogenous Production and Exogenous Administration in Healthy Subjects

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