|
Acute intermittent porphyria
|
0.080 |
AlteredExpression
|
disease |
BEFREE |
Induction of delta aminolevulinic acid synthase 1 ( ALAS1) gene expression and accumulation of neurotoxic intermediates result in neurovisceral attacks and disease manifestations in patients with acute intermittent porphyria, a rare inherited disease of heme biosynthesis.
|
30726693 |
2019 |
|
Acute intermittent porphyria
|
0.080 |
Biomarker
|
disease |
BEFREE |
To introduce next generation sequencing (NGS) to the porphyria diagnosis, we designed a panel that contained four genes, <i>ALAS1, HMBS</i>, <i>CPOX</i> and <i>PPOX</i> for mutational analysis of acute intermittent porphyria (AIP), hereditary coproporphyria (HCP) and variegate porphyria (VP).
|
31154864 |
2019 |
|
Acute intermittent porphyria
|
0.080 |
AlteredExpression
|
disease |
BEFREE |
Levels of clock-controlled gene mRNAs showed significant increases over baseline in all subjects at 5 a.m. and 11 p.m., whereas mRNA levels of ALAS1, ALAS2 and PBGD were increased only at 11 p.m. in subjects with active AIP.
|
23650938 |
2013 |
|
Acute intermittent porphyria
|
0.080 |
Biomarker
|
disease |
BEFREE |
The clinical performance of givosiran revealed that suppression of ALAS1 by GalNac-decorated siRNAs represents an additional approach for the treatment of patients with AIP that manifests recurrent acute neurovisceral attacks.
|
31792921 |
2020 |
|
Acute intermittent porphyria
|
0.080 |
Biomarker
|
disease |
BEFREE |
Altogether, this study has important impacts on AIP care underlying that hemin needs to be restricted to severe neurovisceral crisis and suggests that alternative treatment targeting the liver such as ALAS1 and HO1 inhibitors, and anti-inflammatory therapies should be considered in patients with recurrent AIP.
|
29498764 |
2018 |
|
Acute intermittent porphyria
|
0.080 |
AlteredExpression
|
disease |
BEFREE |
Many interactions and cross-talk take place within the tangle of genomic circuits that control ALAS1-transcription, which may explain the extreme inter- and intra-individual variability in morbidity in acute porphyria.
|
17298222 |
2006 |
|
Acute intermittent porphyria
|
0.080 |
AlteredExpression
|
disease |
BEFREE |
Negative feedback regulation of ALAS-1 by the end product heme is well documented and provides the foundation for heme treatment of acute porphyrias, a group of diseases caused by genetic defects in the heme biosynthesis pathway and exacerbated by controlled up-regulation of ALAS-1.
|
21659532 |
2011 |
|
Acute intermittent porphyria
|
0.080 |
AlteredExpression
|
disease |
BEFREE |
As expected, the ALAS1 expression increased 4.5-fold and 15.9-fold in the WT and AIP mice, respectively.
|
30777612 |
2019 |
|
Adenoma
|
0.010 |
Biomarker
|
group |
BEFREE |
The validation experiment (geNorm) showed that the most stable gene combinations were ALAS1 and GAPDH in NFPA, and PSMC4 and GAPDH in hormone secreting adenomas.
|
27561203 |
2016 |
|
Alzheimer's Disease
|
0.020 |
AlteredExpression
|
disease |
BEFREE |
We found that the expression levels of the rate-limiting heme synthetic enzyme ALAS1 and heme degradation enzyme HO-2 are selectively decreased in AD patients and mice.
|
30723777 |
2019 |
|
Alzheimer's Disease
|
0.020 |
AlteredExpression
|
disease |
BEFREE |
The relative expression of ALAS1 mRNA, the first and rate-limiting enzyme for heme biosynthesis under normal physiological conditions, was significantly (p<0.05) reduced by nearly 90% in AD compared to control.
|
19477221 |
2009 |
|
Bipolar Disorder
|
0.010 |
GeneticVariation
|
disease |
BEFREE |
The meta-analysis between BD and T2D identified six significant SNPs, three of which were located in ALAS1 (best SNP: rs352165, p = 3.4E-08).
|
31754094 |
2019 |
|
Diabetes
|
0.010 |
AlteredExpression
|
disease |
BEFREE |
We evaluated the expression of ALAS1 in a murine model of diabetes and determined the effects of the insulinomimetic vanadate on the enzyme regulation to evaluate its potential for the treatment of acute porphyria attacks.
|
22070747 |
2012 |
|
Diabetes Mellitus
|
0.010 |
AlteredExpression
|
group |
BEFREE |
We evaluated the expression of ALAS1 in a murine model of diabetes and determined the effects of the insulinomimetic vanadate on the enzyme regulation to evaluate its potential for the treatment of acute porphyria attacks.
|
22070747 |
2012 |
|
Diabetes Mellitus, Experimental
|
0.200 |
Biomarker
|
disease |
RGD |
Heme and hemoproteins in streptozotocin-diabetic female rats.
|
6688350 |
1983 |
|
Diabetes Mellitus, Non-Insulin-Dependent
|
0.010 |
GeneticVariation
|
disease |
BEFREE |
The meta-analysis between BD and T2D identified six significant SNPs, three of which were located in ALAS1 (best SNP: rs352165, p = 3.4E-08).
|
31754094 |
2019 |
|
Disorders of Porphyrin Metabolism
|
0.520 |
Biomarker
|
group |
BEFREE |
These results, taken together, permit us to further an INH inhibition kinetic mechanism for ALAS, which suggests the possible use of INH-derived drugs in treating patients with XLPP and potentially other protoporphyrin-accumulating porphyrias.
|
27838491 |
2017 |
|
Disorders of Porphyrin Metabolism
|
0.520 |
Biomarker
|
group |
RGD |
Testing the porphyrinogenicity of propofol in a primed rat model.
|
7547054 |
1995 |
|
Disorders of Porphyrin Metabolism
|
0.520 |
GeneticVariation
|
group |
BEFREE |
In patients, ALAS enzyme activity is affected in most of the mutations causing non-syndromic SA and in several porphyrias.
|
30737140 |
2019 |
|
Disorders of Porphyrin Metabolism
|
0.520 |
Biomarker
|
group |
CTD_human |
Effects of new anticonvulsant medications on porphyrin synthesis in cultured liver cells: potential implications for patients with acute porphyria.
|
9222176 |
1997 |
|
Erythropoietic Protoporphyria
|
0.020 |
AlteredExpression
|
disease |
BEFREE |
Moreover, ALAS2 gain of function mutations is responsible for X-linked protoporphyria and increased ALAS1 activity lead to acute attacks of hepatic porphyrias.
|
30737140 |
2019 |
|
Erythropoietic Protoporphyria
|
0.020 |
GeneticVariation
|
disease |
BEFREE |
In about 2% of patients, overt disease was recently shown to be caused by gain-of-function mutations in the erythroid-specific aminolevulinic acid synthase 2 (ALAS2/ALAS, EC 2.3.1.27) gene and named X-linked dominant protoporphyria.
|
19744342 |
2009 |
|
Hepatitis C
|
0.010 |
AlteredExpression
|
disease |
BEFREE |
Western blot analysis showed a higher expression level of FLVCR1, but not ABCG2, as well as a higher expression level of mature ALAS1, which is the rate-limiting enzyme in the heme synthesis pathway, in HCV core protein-expressing cells compared with controls.
|
29856826 |
2018 |
|
Hereditary Coproporphyria
|
0.010 |
Biomarker
|
disease |
BEFREE |
To introduce next generation sequencing (NGS) to the porphyria diagnosis, we designed a panel that contained four genes, <i>ALAS1, HMBS</i>, <i>CPOX</i> and <i>PPOX</i> for mutational analysis of acute intermittent porphyria (AIP), hereditary coproporphyria (HCP) and variegate porphyria (VP).
|
31154864 |
2019 |
|
Impaired glucose tolerance
|
0.010 |
Biomarker
|
phenotype |
BEFREE |
Mice heterozygous null for ALAS1 (A1+/-s) experience impaired glucose tolerance (IGT) and insulin resistance (IR) beyond 20-weeks of age (aged A1+/-s).
|
29364890 |
2018 |