Onko oligodendrogliassa ALP

ALP pitää substraattina PLP ( aktiviia pyridoksiinia.)

Oligodendroglia  hoitaa aksonin myelinisaatiota.   Aktiivi PLP aktivoi seriinin "aktiiviksi seriiniksi" joka kondensoituu aktiivin palmitiinihapon kanssa myeliinitien esiasteeksi ketosfinganiiniksi, jollioin seriiniosa dekarboksyloituu ja PLP vapautuu. ..

https://www.ncbi.nlm.nih.gov/pubmed/28173571

Neurosurgery. 2017 Feb 1;80(2):248-256. doi: 10.1093/neuros/nyw026.

The Pluripotent Stem-Cell Marker Alkaline Phosphatase is Highly Expressed in Refractory Glioblastoma with DNA Hypomethylation.

Iwadate Y¹, Suganami A², Tamura Y², Matsutani T¹, Hirono S¹, Shinozaki N¹, Hiwasa T³, Takiguchi M³, Saeki N¹.

Abstract

Background:

Hypomethylation of genomic DNA induces stem-cell properties in cancer cells and contributes to the treatment resistance of various malignancies.

Objective:

To examine the correlation between the methylation status of stem-cell-related genes and the treatment outcomes in patients with glioblastoma (GBM).

Methods:

The genome-wide DNA methylation status was determined using HumanMethylation450 BeadChips, and the methylation status was compared between a group of patients with good prognosis (survival > 4 yr) and a group with poor prognosis (survival < 1 yr). Immunohistochemistry for proteins translated from hypomethylated genes, including alkaline phosphatase (ALPL), CD133, and CD44, was performed in 70 GBMs and 60 oligodendroglial tumors.

Results:

The genomic DNA in refractory GBM was more hypomethylated than in GBM from patients with relatively long survival (P = .0111). Stem-cell-related genes including ALPL, CD133, and CD44 were also significantly hypomethylated. A validation study using immunohistochemistry showed that DNA hypomethylation was strongly correlated with high protein expression of ALPL, CD133, and CD44. GBM patients with short survival showed high expression of these stem-cell markers. Multivariate analysis confirmed that co-expression of ALPL + CD133 or ALPL + CD44 was a strong predictor of short survival. Anaplastic oligodendroglial tumors without isocitrate dehydrogenase 1 mutation were significantly correlated with high ALPL expression and poor survival.

Conclusion:

Accumulation of stem-cell properties due to aberrant DNA hypomethylation is associated with the refractory nature of GBM.

KEYWORDS:

Stem cell; Epigenetics; Alkaline phosphatase; ALPL; Antibody microarray; Methylation; GBM; Glioma

 

P-Alp viitearvoista ja kliinisestä merkityksestä , Neuronaali TNAP

Lakartidningen. 2017 Oct 16;114. pii: ETTH.

Tillförlitliga referensintervall krävs för värdering av P-ALP - Nya pediatriska referensintervall för alkaliskt fosfatas har klinisk betydelse för att hitta rätt till diagnosen.

[Article in Swedish]

Magnusson P¹.

Author information

Abstract

Age- and gender-specific reference intervals are pivotal to ensure appropriate interpretation of plasma alkaline phosphatase activities in the lower range Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss-of-function mutations of the ALPL gene that mainly express alkaline phosphatase (ALP) in bone and liver. The clinical expression of HPP is highly variable and is classified into six different forms mainly affecting bone and tooth mineralization. The prognosis for each of these HPP forms depends upon the severity of the skeletal disease which reflects the age at presentation. The biochemical hallmark of HPP is low plasma ALP activity (hypophosphatasemia); however, HPP is often misdiagnosed because of low awareness and sometimes absence of age- and gender-specific ALP reference intervals. Children and adolescents have higher ALP levels in comparison with adults. Reliable reference intervals are pivotal for any clinical laboratory test. Harmonized age- and gender-specific plasma ALP reference intervals ought to be used to ensure appropriate interpretation of plasma ALP activities in the lower range.

http://www.lakartidningen.se/Klinik-och-vetenskap/Kommentar/2017/10/Tillforlitliga-referensintervall-kravs-for-vardering-av-P-ALP/


http://www.socialstyrelsen.se/ovanligadiagnoser/hypofosfatasi#anchor_5



Tästä huomaa että kriittinen kohta fosfaattiaineenvaihdunnassa on sekin että P-ALP käyttää substraattina pyrofosfaatin lisäksi aktiivia B6 vitamiinia jolla on varsin suuri tarve esim myeliinisynteesin aloituksessa. Myeliinin huonosta muodostuksesta tietysti tulee sitä epilepsiaa, johon sitten tehoaa B6- anto jolloin myeliinisynteesi saa alkuainetta aktiivi B6 ja aktiivi seriini kondensoituvat ketosfinganiiniksi jne myeliinitielle se vaatii energiaa tämä synteesitie käsittääkseni. Ilmeisesti  tässä on pahin metabolinen kuoppa koska kyse on samlla keskushermoston kehittymisestä luuston muun fyysisen kehittymisen ohella. Ei tarvitsisi odottaa epileptista kohtausta B6 annon aloitukseen, jos tämä tauti on diagnosoitu.
Siis yksinkertaisesti myeliinia ei muodostu de novo ilman aktiivia B6 vitamiinia.

https://www.ncbi.nlm.nih.gov/pubmed/28072448

https://www.ncbi.nlm.nih.gov/pubmed/22696173

https://www.ncbi.nlm.nih.gov/pubmed/26219720

Subcell Biochem. 2015;76:363-74. doi: 10.1007/978-94-017-7197-9_17.

The Role of Tissue Non-specific Alkaline Phosphatase (TNAP) in Neurodegenerative Diseases: Alzheimer's Disease in the Focus.

Kellett KA¹, Hooper NM.

Abstract

Tissue non-specific alkaline phosphatase (TNAP) is present on neuronal membranes and induces neuronal toxicity via tau dephosphorylation; a mechanism which could play a role in the neuronal loss seen in Alzheimer's disease (AD). TNAP increases in the plasma following brain injury and cerebrovascular disease. In this chapter we summarise our previous work which looked at changes in TNAP activity in the brain and plasma of AD individuals and discuss whether these changes may be reflective of neuronal loss. Our data demonstrate that TNAP activity is significantly increased in the brain in both the sporadic and familial forms of AD and that TNAP activity is significantly increased in the plasma in AD patients. In addition, we describe a significant inverse correlation between plasma TNAP activity and cognitive function in AD. Using these data we propose a model for TNAP-induced neurodegeneration in AD resulting from tau dephosphorylation following secretion of tau from neuronal cells.

PMID:

26219720

DOI:

10.1007/978-94-017-7197-9_17

[Indexed for MEDLINE]

PTEN ja SPRY-1 Duchennen lihasdystrofiassa kohdegeenejä.

https://www.ncbi.nlm.nih.gov/pubmed/25892183

Biochim Biophys Acta. 2015 Jul;1852(7):1451-64. doi: 10.1016/j.bbadis.2015.04.013. Epub 2015 Apr 17.

Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy.

Zanotti S¹, Gibertini S¹, Curcio M¹, Savadori P¹, Pasanisi B¹, Morandi L¹, Cornelio F¹, Mantegazza R¹, Mora M².

Abstract

Excessive extracellular matrix deposition progressively replacing muscle fibres is the endpoint of most severe muscle diseases. Recent data indicate major involvement of microRNAs in regulating pro- and anti-fibrotic genes. To investigate the roles of miR-21 and miR-29 in muscle fibrosis in Duchenne muscle dystrophy, we evaluated their expression in muscle biopsies from 14 patients, and in muscle-derived fibroblasts and myoblasts. In Duchenne muscle biopsies, miR-21 expression was significantly increased, and correlated directly with COL1A1 and COL6A1 transcript levels. MiR-21 expression was also significantly increased in Duchenne fibroblasts, more so after TGF-β1 treatment. In Duchenne fibroblasts the expression of miR-21 target transcripts PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SPRY-1 (Sprouty homolog 1) was significantly reduced; while collagen I and VI transcript levels and soluble collagen production were significantly increased. MiR-29a and miR-29c were significantly reduced in Duchenne muscle and myoblasts, and miR-29 target transcripts, COL3A1, FBN1 and YY1, significantly increased. MiR-21 silencing in mdx mice reduced fibrosis in the diaphragm muscle and in both Duchenne fibroblasts and mdx mice restored PTEN and SPRY-1 expression, and significantly reduced collagen I and VI expression; while miR-29 mimicking in Duchenne myoblasts significantly decreased miR-29 target transcripts. These findings indicate that miR-21 and miR-29 play opposing roles in Duchenne muscle fibrosis and suggest that pharmacological modulation of their expression has therapeutic potential for reducing fibrosis in this condition.

Copyright © 2015. Published by Elsevier B.V.

KEYWORDS:

Duchenne muscular dystrophy; Fibroblast; Fibrosis; MiR-21; MiR-29; Myoblast; mdx mouse

PMID:

25892183

DOI:

10.1016/j.bbadis.2015.04.013

[Indexed for MEDLINE]

Free full text

• Highlights

  •

  MiR-21 is increased in DMD patient muscle and fibroblasts and its target genes PTEN and SPRY-1 are reduced.

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  MiR-21 silencing in DMD fibroblasts and mdx mice restores PTEN and SPRY-1 levels.

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  MiR-29a and miR-29c are reduced in DMD muscle and myoblasts.

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  MiR-29 mimicking in DMD myoblasts significantly decreases miR-29 target genes.

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  MiR-21 and miR-29 play opposing roles in muscl
  
  

  GeneCards Summary for SPRY1 Gene

  SPRY1 (Sprouty RTK Signaling Antagonist 1) is a Protein Coding gene. Diseases associated with SPRY1 include Adrenal Cortical Adenocarcinoma and Legius Syndrome. Among its related pathways are Signaling by GPCR and Angiogenesis (CST). An important paralog of this gene is SPRY2.