Last update 01 Nov 2024

ALDH1A2

Last update 01 Nov 2024

Basic Info

Synonyms

aldehyde dehydrogenase 1 family member A2, Aldehyde dehydrogenase family 1 member A2, ALDH1A2

+ [5]

Introduction

Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively (PubMed:29240402, PubMed:33565183). Retinoate signaling is critical for the transcriptional control of many genes, for instance it is crucial for initiation of meiosis in both male and female (PubMed:33565183) (Probable). Recognizes retinal as substrate, both in its free form and when bound to cellular retinol-binding protein (By similarity). Can metabolize octanal and decanal, but has only very low activity with benzaldehyde, acetaldehyde and propanal (By similarity). Displays complete lack of activity with citral (By similarity).

Drugs associated with ALDH1A2

ABD-3001

Target

ALDH1A1 x ALDH1A2

Mechanism

ALDH1A1 inhibitors [+1]

Active Org.

Advanced BioDesign SAS [+2]

Originator Org.

Advanced BioDesign SAS

Active Indication

Adult Acute Myeloblastic Leukemia [+8]

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with ALDH1A2

NCT05601726 / RecruitingPhase 1

First-In-Human, Open Label, Dose Escalation Study to Evaluate Safety, PK and PD of ABD-3001 as Monotherapy in Relapsed/Refractory Acute Myeloid Leukemia or High/Very-high Risk Myelodysplastic Syndromes Patients, Ineligible for Intensive or New Generation Targeted Therapy.

This First In Human (FIH) study is a prospective, open-label, multicenter, Phase 1 study, with a dose escalation design, followed by an optimized design. It will consist in a Single Ascending Dose (SAD) part and a Multiple Ascending Dose (MAD) part followed by a "Regimen optimization" part with an extension cohort.

Start Date08 Nov 2022

Sponsor / Collaborator

Advanced BioDesign SAS

100 Clinical Results associated with ALDH1A2

100 Translational Medicine associated with ALDH1A2

0 Patents (Medical) associated with ALDH1A2

668

Literatures (Medical) associated with ALDH1A2

01 Dec 2024·Journal of Affective Disorders

Altered transcriptomes, cell type proportions, and dendritic spine morphology in hippocampus of suicide decedents

Article

Author: Williams, Megan E ; Panicker, Mitradas M ; Vawter, Marquis P ; Christensen, Erik D ; Bunney, William E ; Coon, Hilary ; Callor, William B ; Jerominski, Leslie ; Schulmann, Anton ; Das, Sujan C

BACKGROUNDSuicide is a manner of death resulting from complex environmental and genetic risks that affect millions of people globally. Both structural and functional studies identified the hippocampus as one of the vulnerable brain regions contributing to suicide risk.METHODSWe have identified the hippocampal tissue transcriptomes, gene ontology, cell type proportions, and dendritic spine morphology in controls (n = 28) and suicide decedents (n = 22). In addition, the transcriptomic signature in iPSC-derived neuronal precursor cells (NPCs) and neurons were also investigated in controls (n = 2) and suicide decedents (n = 2).RESULTSThe hippocampal tissue transcriptomic data revealed that NPAS4 gene expression was downregulated while ALDH1A2, NAAA, and MLXIPL gene expressions were upregulated in hippocampal tissue of suicide decedents. The gene ontology identified 29 significant pathways including NPAS4-associated gene ontology terms "excitatory post-synaptic potential", "regulation of postsynaptic membrane potential" and "long-term memory" indicating alteration of glutamatergic synapses in the hippocampus of suicide decedents. The cell type deconvolution identified decreased excitatory neuron proportion and an increased inhibitory neuron proportion providing evidence of excitation/inhibition imbalance in the hippocampus of suicide decedents. In addition, suicide decedents had increased dendric spine density in the hippocampus, due to an increase of thin (relatively unstable) dendritic spines, compared to controls. The transcriptomes of iPSC-derived hippocampal-like NPCs and neurons revealed 31 and 33 differentially expressed genes in NPC and neurons, respectively, of suicide decedents.CONCLUSIONSOur findings will provide new insights into the hippocampal neuropathology of suicide.

18 Oct 2024·Orphanet journal of rare diseases

Toll-like receptors ligand immunomodulators for the treatment congenital diaphragmatic hernia.

Article

Author: Salvador, Beatriz ; Llamas, Miguel Ángel ; Tovar, Juan Antonio ; Muñoz-Chápuli, Ramón ; Vallejo-Cremades, Mayte ; Martínez, Leopoldo ; Merino, Javier ; Fresno, Manuel ; Carmona, Rita ; Córdoba, Laura

BACKGROUNDCongenital diaphragmatic hernia (CDH) is a rare disease that affects the development of the diaphragm, leading to abnormal lung development. Unfortunately, there is no established therapy for CDH. Retinoic acid pathways are implicated in the ethology of CDH and macrophages are known to play a role in repairing organ damage.METHODSWe have analyzed the effect of several Toll like receptor (TLR) ligands in the nitrofen-induced CDH model in pregnant rats widely used to study this disease and in the G2-GATA4^Cre;Wt1^fl/fl CDH genetic mice model. Morphometric and histological studies were carried out. Immune cell infiltration was assayed by immunochemistry and immunofluorescence and retinoic pathway gene expression analyzed in vivo and in vitro in macrophages.RESULTSWe found that administering a single dose of atypical TLR2/4 ligands (CS1 or CS2), 3 days after nitrofen, cured diaphragmatic hernia in 73% of the fetuses and repaired the lesion with complete diaphragm closure being on the other hand nontoxic for the mothers or pups. Moreover, these immunomodulators also improved pulmonary hypoplasia and alveolar maturation and vessel hypertrophy, enhancing pulmonary maturity of fetuses. We also found that CS1 treatment rescued the CDH phenotype in the G2-GATA4^Cre;Wt1^fl/fl CDH genetic mice model. Only 1 out of 11 mutant embryos showed CDH after CS1 administration, whereas CDH prevalence was 70% in untreated mutant embryos. Mechanistically, CS1 stimulated the infiltration of repairing M2 macrophages (CD206⁺ and Arg1⁺) into the damaged diaphragm and reduced T cell infiltration. Additionally, those TLR ligands induced retinol pathway genes, including RBP1, RALDH2, RARα, and RARβ, in the affected lungs and the diaphragm and in macrophages in vitro.CONCLUSIONSOur research has shown that TLR ligand immunomodulators that influence anti-inflammatory macrophage activation can be effective in treating CDH, being nontoxic for the mothers or pups suggesting that those TLR ligands are a promising solution for CDH leading to orphan drug designation for CS1. The immune system of the fetus would be responsible for repairing the damage and closure of the hernia in the diaphragm and enhanced proper lung development after CS1 treatment.

01 Oct 2024·The Journal of Steroid Biochemistry and Molecular Biology

Seasonal changes in vitamin A metabolism-related factors in the oviduct of Chinese brown frog (Rana dybowskii)

Article

Author: Liu, Yuning ; Chen, Haohan ; Wang, Yawei ; Wang, Yankun ; Zhang, Haolin ; Xu, Meiyu ; Weng, Qiang

The oviduct of the Chinese brown frog (Rana dybowskii) expands during pre-brumation rather than the breeding period, exhibiting a special physiological feature. Vitamin A is essential for the proper growth and development of many organisms, including the reproductive system such as ovary and oviduct. Vitamin A is metabolized into retinoic acid, which is crucial for oviduct formation. This study examined the relationship between oviducal expansion and vitamin A metabolism. We observed a significant increase in the weight and diameter of the oviduct in Rana dybowskii during pre-brumation. Vitamin A and its active metabolite, retinoic acid, notably increased during pre-brumation. The mRNA levels of retinol binding protein 4 (rbp4) and its receptor stra6 gene, involved in vitamin A transport, were elevated during pre-brumation compared to the breeding period. In the vitamin A metabolic pathway, the mRNA expression level of retinoic acid synthase aldh1a2 decreased significantly during pre-brumation, while the mRNA levels of retinoic acid α receptor (rarα) and the retinoic acid catabolic enzyme cyp26a1 increased significantly during pre-brumation, but not during the breeding period. Immunohistochemical results showed that Rbp4, Stra6, Aldh1a2, Rarα, and Cyp26a1 were expressed in ampulla region of the oviduct. Western blot results indicated that Aldh1a2 expression was lower, while Rbp4, Stra6, RARα, and Cyp26a1 were higher during pre-brumation compared to the breeding period. Transcriptome analyses further identified differential genes in the oviduct and found enrichment of differential genes in the vitamin A metabolism pathway, providing evidences for our study. These results suggest that the vitamin A metabolic pathway is more active during pre-brumation compared to the breeding period, and retinoic acid may regulate pre-brumation oviductal expansion through Rarα-mediated autocrine/paracrine modulation.

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ALDH1A2

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