D-Serine - Revision history

Roel Van de Paar at 04:20, 27 June 2017

2017-06-27T04:20:50Z

Roel Van de Paar at 04:20, 27 June 2017

2017-06-27T04:20:36Z

Roel Van de Paar at 04:19, 27 June 2017

2017-06-27T04:19:14Z

Roel Van de Paar: /* Other interesting links */

2017-04-28T05:54:22Z

‎Other interesting links

Roel Van de Paar: /* Other interesting links */

2017-04-28T05:54:03Z

‎Other interesting links

Roel Van de Paar: /* D-Serine and NMDA Receptors */

2017-04-28T05:31:52Z

‎D-Serine and NMDA Receptors

Roel Van de Paar at 05:30, 28 April 2017

2017-04-28T05:30:35Z

Roel Van de Paar: /* Hypothesis */

2017-04-20T04:10:21Z

‎Hypothesis

Roel Van de Paar: /* Hypothesis */

2017-04-20T04:05:33Z

‎Hypothesis

Roel Van de Paar: /* D-Serine and NMDA Receptors */

2017-04-20T04:04:44Z

‎D-Serine and NMDA Receptors

@@ Line 27: / Line 27: @@
 == Other interesting links ==
 * Schizophrenia, symptoms - https://www.sane.org/mental-health-and-illness/facts-and-guides/schizophrenia<br />
 * OCD, Glycine - https://www.hindawi.com/archive/2014/859735/<br />
 * Oxidation & it's results - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964749/#R37

@@ Line 27: / Line 27: @@
 == Other interesting links ==
-Schizophrenia, symptoms - https://www.sane.org/mental-health-and-illness/facts-and-guides/schizophrenia<br />
+* [[Oxidative Stress]]
-OCD, Glycine - https://www.hindawi.com/archive/2014/859735/<br />
+* Schizophrenia, symptoms - https://www.sane.org/mental-health-and-illness/facts-and-guides/schizophrenia<br />
-Oxidation & it's results - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964749/#R37
+* OCD, Glycine - https://www.hindawi.com/archive/2014/859735/<br />
 == '''Hypothesis''' ==

← Older revision		Revision as of 04:19, 27 June 2017
Line 25:		Line 25:

	''Define: excitotoxicity:'' Excitotoxicity is the pathological process by which nerve cells are damaged or killed by excessive stimulation by neurotransmitters such as glutamate and similar substances.<ref>Excitotoxicity,wikipedia,https://en.wikipedia.org/wiki/Excitotoxicity</ref>		''Define: excitotoxicity:'' Excitotoxicity is the pathological process by which nerve cells are damaged or killed by excessive stimulation by neurotransmitters such as glutamate and similar substances.<ref>Excitotoxicity,wikipedia,https://en.wikipedia.org/wiki/Excitotoxicity</ref>
−
−	~~== Oxidative Stress ==~~
−
−	~~'''Oxidative stress theory for adult onset of psychosis:'''~~
−
−	Oxidative stresses gradually increase until GSH (Glutathione) and MT (Metallothionein) proteins are overwhelmed, resulting in sudden brain inflammation, alteration of NT (neurotransmitter) levels, and disruption of the blood brain barrier. As in Wilson’s Disease, sudden onset of a mental illness in young adulthood may result.<ref name=walsh_imbalances>Biochemical imbalances in mental health populations, William J. Walsh PhD, Walsh Institute, http://www.walshinstitute.org/uploads/1/7/9/9/17997321/biochemical_imbalances_in_mental_health_populations.pdf</ref>
−
−	''Define: psychosis:'' a severe mental disorder in which thought and emotions are so impaired that contact is lost with external reality.<ref>define: psychosis, Google, https://www.google.com/search?q=define%3Apsychosis</ref>
−
−	~~All major phenotypes of schizophrenia involve severe oxidative stress, [and] oxidative overload depletes GSH and reduces glutamate activity at NMDA receptors.<ref name="walsh_imbalances" />~~
−
−	Abnormal methylation and severe oxidative stress are major causes of epigenetic errors, [and] greater than 95% of schizophrenics exhibit abnormal methylation or oxidative overload.<ref name="walsh_imbalances" />
−
−	''Define: schizophrenia:'' a long-term mental disorder of a type involving a breakdown in the relation between thought, emotion, and behaviour, leading to faulty perception, unfitting actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation.<ref>define: schizophrenia, Google, https://www.google.com/search?q=define%3Aschizophrenia (edited)</ref>

	== Other interesting links ==		== Other interesting links ==

@@ Line 42: / Line 42: @@
 == Other interesting links ==
 Schizophrenia, symptoms - https://www.sane.org/mental-health-and-illness/facts-and-guides/schizophrenia<br />
-OCD, Glycine - https://www.hindawi.com/archive/2014/859735/
+OCD, Glycine - https://www.hindawi.com/archive/2014/859735/<br />
 Oxidation & it's results - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964749/#R37

@@ Line 43: / Line 43: @@
 Schizophrenia, symptoms - https://www.sane.org/mental-health-and-illness/facts-and-guides/schizophrenia<br />
 OCD, Glycine - https://www.hindawi.com/archive/2014/859735/
 == '''Hypothesis''' ==

@@ Line 10: / Line 10: @@
 ''Define: hypofunction:'' Reduced, low, or inadequate function.<ref>Farlex Partner Medical Dictionary,© Farlex 2012</ref>
 '''D-Serine''' is an <u>obligatory endogenous coagonist</u> of the NMDA receptor, functioning in vivo as a specific and potent full agonist at the NMDAR-associated glycine modulatory site.<ref>''D-Serine in Neuropsychiatric Disorders: New Advances'',Hindawi,https://www.hindawi.com/archive/2014/859735/</ref>
@@ Line 15: / Line 19: @@
 ''Define: endogenous:'' (biology) growing or originating from within an organism.<ref>Define: endogenous,Google,https://www.google.com/search?q=define%3Aendogenous</ref><br />
 ''Define: co-agonist:'' (biochemistry) A drug or other chemical that can combine with a receptor on a cell to produce a physiologic reaction typical of a naturally occurring substance. Co-agonist implies it is one of other agonists working in conjunction.<ref>co-agonist,wiktionary,https://en.wiktionary.org/wiki/co-agonist</ref><br />
 In addition to alleviating several diseases and conditions, '''D-serine''' may have its dark side in neurodegenerative disease.<ref name="D-Serine_other_side">D-serine as a gliotransmitter and its roles in brain development and disease,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632749/</ref> D-serine may play a role in excitotoxic neuronal death in Alzheimer’s disease and also in amyotrophic lateral sclerosis (ALS) as a principal cause for motoneuron death (considered to be excitotoxicity).<ref name="D-Serine_other_side"></ref> 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.<ref name="D-Serine_other_side"></ref> 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.<ref name="D-Serine_other_side"></ref>
@@ Line 22: / Line 25: @@
 ''Define: excitotoxicity:'' Excitotoxicity is the pathological process by which nerve cells are damaged or killed by excessive stimulation by neurotransmitters such as glutamate and similar substances.<ref>Excitotoxicity,wikipedia,https://en.wikipedia.org/wiki/Excitotoxicity</ref>
 == Oxidative Stress ==

← Older revision		Revision as of 05:30, 28 April 2017
Line 22:		Line 22:

	''Define: excitotoxicity:'' Excitotoxicity is the pathological process by which nerve cells are damaged or killed by excessive stimulation by neurotransmitters such as glutamate and similar substances.<ref>Excitotoxicity,wikipedia,https://en.wikipedia.org/wiki/Excitotoxicity</ref>		''Define: excitotoxicity:'' Excitotoxicity is the pathological process by which nerve cells are damaged or killed by excessive stimulation by neurotransmitters such as glutamate and similar substances.<ref>Excitotoxicity,wikipedia,https://en.wikipedia.org/wiki/Excitotoxicity</ref>
		+
		+	D-Serine, synthesized in the brain by serine racemase from L-serine (its enantiomer), serves as a neuromodulator by coactivating NMDA receptors, making them able to open if they then also bind glutamate. D-serine is a potent agonist at the glycine site of the NMDA-type glutamate receptor (NMDAR). For the receptor to open, glutamate and either glycine or D-serine must bind to it; in addition a pore blocker must not be bound (e.g. Mg2+ or Pb2+).[11] In fact, D-serine is a more potent agonist at the glycine site on the NMDAR than glycine itself.<ref>Serine,Wikipedia,https://en.wikipedia.org/wiki/Serine</ref>

	== Oxidative Stress ==		== Oxidative Stress ==

@@ Line 43: / Line 43: @@
 == '''Hypothesis''' ==
 * Increasing D-serine levels may help to overcome cognitive impairments related to the dysfunction of NMDAR signaling.
-* Increasing D-serine levels
+* Increasing D-serine levels may cause NMDAR-dependent damage.
 == References ==
 <references />

@@ Line 17: / Line 17: @@
 ''Define: agonist:'' (biochemistry) A molecule that can combine with a receptor on a cell to produce a physiological reaction.<ref>agonist,wiktionary,https://en.wiktionary.org/wiki/agonist</ref>
-In addition to alleviating several diseases and conditions, D-serine may have its dark side in neurodegenerative disease.<ref name="D-Serine_other_side">D-serine as a gliotransmitter and its roles in brain development and disease,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632749/</ref> D-serine may play a role in excitotoxic neuronal death in Alzheimer’s disease and also in amyotrophic lateral sclerosis (ALS) as a principal cause for motoneuron death (considered to be excitotoxicity).<ref name="D-Serine_other_side"></ref> 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.<ref name="D-Serine_other_side"></ref> 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.<ref name="D-Serine_other_side"></ref>
+In addition to alleviating several diseases and conditions, '''D-serine''' may have its dark side in neurodegenerative disease.<ref name="D-Serine_other_side">D-serine as a gliotransmitter and its roles in brain development and disease,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632749/</ref> D-serine may play a role in excitotoxic neuronal death in Alzheimer’s disease and also in amyotrophic lateral sclerosis (ALS) as a principal cause for motoneuron death (considered to be excitotoxicity).<ref name="D-Serine_other_side"></ref> 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.<ref name="D-Serine_other_side"></ref> 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.<ref name="D-Serine_other_side"></ref>
 It is conceivable that '''D-serine''' signalling could be involved in brain disorders in which NMDARs contributes to the pathophysiology, such as stroke. Here, an indirect reduction of NMDAR-mediated excitotoxicity through modified D-serine supply may in principle suggest new therapeutic avenues. It is encouraging in that respect that SR deletion (i.e. serine racemase (SR), which converts L-serine to D-serine) was recently reported to reduce tissue damage in a mouse stroke model (Mustafa et al., 2010). However, increasing D-serine levels might on the other hand help to overcome cognitive impairments related to the dysfunction of NMDAR signaling. Promising early studies showed that '''Dcycloserine''', a partial agonist at the NMDAR co-agonist site, can improve spatial learning in rats (Monahan et al., 1989). Therapeutic approaches targeting D-serine signaling will therefore have to strike the balance between preventing NMDAR-dependent damage and avoiding cognitive impairment.<ref>D-Serine: A key to synaptic plasticity?,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375648/pdf/ukmss-48553.pdf</ref>