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L-Serine Conclusion?

d-serine microglia alzheimers l-serine serine dementia

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#1 Sicko

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Posted 20 April 2020 - 11:39 PM

Edit: The post title uses l-serine, but all of the studies I referenced with bad conclusions are studying d-serine. All of the studies I referenced with good conclusions are talking about l-serine.


I don't know what to think about some conflicting things I've read about d-serine. On one hand, I just read about l-serine (which d-serine is derived from) being protective against Alzheimer's by preventing BMAA accumulation and subsequent misfolding of proteins. But I also came across studies that indicated d-serine in microglial activation related to Alzheimer's. 


I linked some studies below. What do you think the consensus is? Is the helpfulness of d-serine in general dependent on the specific conditions in each person, whether the dementia or Alzheimer's is caused by the BMAA or by inflammation and microglial activation? Are the studies implicating d-serine negatively in Alzheimer's pathology missing a link that would eliminate the conclusion of the downsides and detrimental effects of d-serine in the condition?


Is supplementing l-serine instead of d-serine very different in these potential negative implications of d-serine? I ask because I just got some l-serine powder after reading the positives of it for dementia and Alzheimer's.





Impact of Aging in Microglia-Mediated D-Serine Balance in the CNS - https://www.hindawi....i/2018/7219732/

"Given that inflammatory activation of microglia promotes increased release of D-serine, we postulate that age-dependent inflammatory brain environment leads to microglia-mediated changes on the D-serine-regulated glutamatergic transmission. Furthermore, D-serine dysregulation, in addition to affecting synaptogenesis and synaptic plasticity, appears also to potentiate NMDAR-dependent excitotoxicity, promoting neurodegeneration and cognitive impairment. D-serine dysregulation promoted by microglia could have a role in age-related cognitive impairment and in the induction and progression of neurodegenerative processes like Alzheimer’s disease."


D-serine as a gliotransmitter and its roles in brain development and disease - https://www.frontier...2013.00039/full

"Neurodegenerative Disorders: the Dark Side of D-Serine

In addition to alleviating several diseases and conditions, D-serine may have its dark side in neurodegenerative disease. Amyloid beta (Aβ) and secreted amyloid precursor protein appear to induce the release of D-serine and glutamate from cultured microglia by increasing transcription and stabilization of the microglial SR (Wu et al., 2004). This could contribute to excitotoxic neuronal death in Alzheimer’s disease. D-serine may play a similar role in amyotrophic lateral sclerosis (ALS) where a principal cause for motoneuron death is considered to be excitotoxicity (Bruijn et al., 2004). The cerebrospinal fluid of ALS patients has been reported to contain elevated glutamate levels (Rothstein et al., 1990). Interestingly, it has been observed that spinal cord in the G93A-SOD1 transgenic mouse model for ALS has several-fold higher concentrations of D-serine than control animals (Sasabe et al., 2007). In these mice, D-serine was found to be produced by activated microglia. The presence of endogenous D-serine has been shown to be necessary for most, if not all, NMDAR-mediated excitotoxicity observed in rat brain slices and in vivo (Katsuki et al., 2004; Hama et al., 2006; Inoue et al., 2008). Pretreatment of rat hippocampal organotypic slices with D-serine deaminase was shown to practically abolish NMDA-mediated excitotoxicity, suggesting that D-serine, rather than glycine, participates in these excitotoxic events in the hippocampus (Shleper et al., 2005). Furthermore, SR knockout mice exhibited a 50–60% reduction in the volume of brain damaged in a transient cerebral artery occlusion-induced stroke model. These SR knockout mice were protected against focal cerebral ischemia despite a fourfold increase in NR1 subunits and elevated NMDAR sensitivity (Mustafa et al., 2010). D-serine has also been hypothesized to participate in epileptogenesis. In animals with pilocarpine-induced epilepsy increased D-serine content in astroglia or neurons, but interestingly not microglia, has been reported (Liu et al., 2009)."
Induction of serine racemase expression and D-serine release from microglia by amyloid β-peptide - https://jneuroinflam...6/1742-2094-1-2
"Conditioned medium from Aβ-treated microglia contained elevated levels of D-serine. Bioassays of hippocampal neurons with the microglia-conditioned medium indicated that Aβ elevated a NMDA receptor agonist that was sensitive to an antagonist of the D-serine/glycine site (5,7-dicholorokynurenic acid; DCKA) and to enzymatic degradation of D-amino acids by D-amino acid oxidase (DAAOx). In the microglia, Aβ elevated steady-state levels of dimeric serine racemase, the apparent active form of the enzyme. Promoter-reporter and mRNA analyses suggest that serine racemase is transcriptionally induced by Aβ. Finally, the levels of serine racemase mRNA were elevated in Alzheimer's disease hippocampus, relative to age-matched controls.


These data suggest that Aβ could contribute to neurodegeneration through stimulating microglia to release cooperative excitatory amino acids, including D-serine."


D-Serine Is the Dominant Endogenous Coagonist for NMDA Receptor Neurotoxicity in Organotypic Hippocampal Slices - https://www.jneurosc...25/41/9413.long
"We report that complete removal of d-serine virtually abolished NMDA-elicited neurotoxicity but did not protect against kainate. Although levels of glycine were 10-fold higher than d-serine, endogenous glycine was ineffective in mediating NMDA receptor neurotoxicity. The effect of endogenous glycine could be observed only after simultaneous removal of endogenous d-serine and blockage of the glycine transporter GlyT1. Our data indicate that d-serine is the dominant coagonist for NMDA receptor-elicited neurotoxicity, mediating all cell death elicited by NMDA in organotypic slices. The results suggest an essential role for this unusual d-amino acid, with implications for the mechanism of neuronal death in the nervous system."
Don't know how to interpret:
Possible role of D-serine in the pathophysiology of Alzheimer's disease - https://www.ncbi.nlm...pubmed/14751437
"Several lines of evidence suggest that D-serine may function as an endogenous agonist of the glycine site on the N-methyl-D-aspartate (NMDA) receptor that has been implicated in the pathophysiology of Alzheimer's disease (AD). The purpose of the study was to determine whether serum levels of D- and L-serine in patients with AD are altered as compared with normal controls. Serum levels of D- and L-serine in patients of AD and age- and gender-matched normal controls were determined using a high-performance liquid chromatography (HPLC). Serum levels of D-serine in the patients with AD were slightly (z=-1.77, p=0.078) lower than those of normal controls. In contrast, serum levels of L-serine in the patients were slightly (z=-1.73, p=0.083) higher than those of controls. In addition, the percentage (%) of D-serine in the total (L+D) serine in the patients was significantly (z=-2.36, p=0.018) lower than that of controls. The present study suggests that the reduced activity of serine racemase, an enzyme catalyzing the formation of D-serine from L-serine may play a role in the pathophysiology of AD."
(Yahoo Finance Article) Could This Radical New Approach to Alzheimer’s Lead to a Breakthrough? - https://finance.yaho...-113033328.html
"Here’s what we now think is astonishing about ­L-serine,” Cox said. “It appears to be neuroprotective against all possible protein misfolding. It basically turns on a system in our brains that looks for unfolded proteins and is quickly poised to act on them.”
Long-Term L-Serine Administration Reduces Food Intake and Improves Oxidative Stress and Sirt1/NFκB Signaling in the Hypothalamus of Aging Mice - https://www.frontier...2018.00476/full
"Moreover, the administration of 0.5% L-serine decreased the concentrations of leptin, malondialdehyde, interleukin-1β, and interleukin-6, while it increased those of superoxide dismutase and glutathione, in both the serum and hypothalamus. Reactive oxygen species and the activity of nicotinamide adenine dinucleotide phosphate oxidase were reduced in the hypothalamus of aging mice treated with L-serine as compared with untreated control mice. Additionally, the expression of the leptin receptor increased while the levels of neuropeptide Y and agouti-related protein decreased in mice that had been treated with 0.5% L-serine. The expression of Sirt1 and phosphorylated signal transducers and activators of transcription 3 (pSTAT3) increased, while that of phosphorylated NFκB decreased in the mice treated with 0.5% L-serine. These results indicated that long-term L-serine administration reduces body weight by decreasing orexigenic peptide expression and reduces oxidative stress and inflammation during aging in mice, possibly by modulating the Sirt1/NFκB pathway. Thus, L-serine has the potential to be used in the prevention of age-related obesity."
Reduction of inflammatory responses by L-serine treatment leads to neuroprotection in mice after traumatic brain injury. - https://www.ncbi.nlm...pubmed/25747604
"We found l-serine treatment: 1) decreased the neurological deficit score, brain water content, lesion volume, and neurone loss; 2) inhibited activated caspase-3; and 3) reduced the levels of TNF-α, IL-1β and IL-6 and the number of GFAP- and Iba-1-positive cells. The effects of l-serine were antagonised by the administration of strychnine, an antagonist of glycine receptors. In addition, we found that glycine receptors were expressed mainly in the cortical neurones but less in the astrocytes or microglial cells, and l-serine activated these receptors and induced strychnine-sensitive currents in these neurones. In conclusion, l-serine induces the activation of glycine receptors, which alleviates neuronal excitotoxicity, a secondary brain injury process, thereby reduces the activation of astrocytes and microglial cells and secretion of proinflammatory cytokines and inhibits neuronal apoptosis. Thus, l-serine treatment leads to neuroprotection of brain tissue through reducing inflammatory responses and improves recovery of the neurological functions in mice after traumatic brain injury."


Edited by Sicko, 20 April 2020 - 11:50 PM.

#2 lancebr

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Posted 27 September 2020 - 02:57 AM

Have you found an answer to your question as to if l-serine is good to take for Alzheimer?

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