Last update 01 Nov 2024

ALDH1A3

Last update 01 Nov 2024

Basic Info

Synonyms

aldehyde dehydrogenase 1 family member A3, Aldehyde dehydrogenase 6, Aldehyde dehydrogenase family 1 member A3

+ [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 (By similarity) (PubMed:27759097). High specificity for all-trans-retinal as substrate, can also accept acetaldehyde as substrate in vitro but with lower affinity (PubMed:27759097). Required for the biosynthesis of normal levels of retinoate in the embryonic ocular and nasal regions; a critical lipid in the embryonic development of the eye and the nasal region (By similarity).

Drugs associated with ALDH1A3

NR6

Target

ALDH1A3

Mechanism

ALDH1A3 inhibitors

Active Org.

Università degli Studi del Piemonte Orientale Amedeo Avogadro

Originator Org.

Università degli Studi del Piemonte Orientale Amedeo Avogadro

Active Indication

Malignant Pleural Mesothelioma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

D34-919

Target

ALDH1A3 x PKM2

Mechanism

ALDH1A3 modulators [+1]

Active Org.

Capital University of Medical Sciences

Originator Org.

Capital University of Medical Sciences

Active Indication

Glioblastoma

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ALDH1A3

100 Translational Medicine associated with ALDH1A3

0 Patents (Medical) associated with ALDH1A3

506

Literatures (Medical) associated with ALDH1A3

01 Dec 2024·Non-coding RNA Research

Circular RNA LMBR1 inhibits bladder cancer progression by enhancing expression of the protein ALDH1A3

Article

Author: Huang, Yapeng ; Lv, Yifan ; Zhu, Xiaowei ; Yuan, Zusen ; Chen, Dongmao ; Qi, Defeng ; Ji, Weidong ; Ying, Xiaoling ; Chen, Zhibin

BackgroundCircular RNAs (circRNAs) have been identified as playing an integral role in the development of bladder cancer (BC). However, the mechanism by which circRNAs operate in the chemical carcinogenesis of BC remains unclear.MethodsTo explore this mechanism, we used RNA high-throughput sequencing to identify differentially expressed circRNA in bladder epithelial cells and chemically induced malignant transformed BC cells. Subsequently, in vitro experiments were conducted to investigate the biological function and molecular mechanism of circLMBR1 in BC. Finally, animal experiments were conducted to examine the clinical relevance of circLMBR1 in vivo.ResultsOur profiling of circular RNA expression during cellular malignant transformation induced by chemical carcinogens identified a subset of circRNAs associated with cell transformation. We verified that the expression of circLMBR1 in bladder epithelial malignant transformed cells was decreased compared with control cells, as well as in BC tissues and bladder cell lines. Furthermore, circLMBR1 was seen to inhibit the proliferation, invasion, and migration of BC cells both in vitro and in vivo. Mechanistically, circLMBR1 was found to exert its antitumor effect by binding to the protein ALDH1A3.ConclusionsOur findings have revealed that circLMBR1 inhibits the progression of BC cells by binding to ALDH1A3 and upregulating its expression. As such, circLMBR1 serves as a promising predictor of BC and may provide a novel therapeutic target for the treatment of BC.

01 Dec 2024·Metabolic Engineering Communications

A comparative analysis of NADPH supply strategies in Saccharomyces cerevisiae: Production of d-xylitol from d-xylose as a case study

Article

Author: Weuster-Botz, Dirk ; Oreb, Mislav ; Knesebeck, Melanie ; Boles, Eckhard ; Regmi, Priti

Enhancing the supply of the redox cofactor NADPH in metabolically engineered cells is a critical target for optimizing the synthesis of many product classes, such as fatty acids or terpenoids. In S. cerevisiae, several successful approaches have been developed in different experimental contexts. However, their systematic comparison has not been reported. Here, we established the reduction of xylose to xylitol by an NADPH-dependent xylose reductase as a model reaction to compare the efficacy of different NADPH supply strategies in the course of a batch fermentation, in which glucose and ethanol are sequentially used as carbon sources and redox donors. We show that strains overexpressing the glucose-6-phosphate dehydrogenase Zwf1 perform best, producing up to 16.9 g L^-1 xylitol from 20 g L^-1 xylose in stirred tank bioreactors. The beneficial effect of increased Zwf1 activity is especially pronounced during the ethanol consumption phase. The same notion applies to the deletion of the aldehyde dehydrogenase ALD6 gene, albeit at a quantitatively lower level. Reduced expression of the phosphoglucose isomerase Pgi1 and heterologous expression of the NADP⁺-dependent glyceraldehyde-3-phosphate dehydrogenase Gdp1 from Kluyveromyces lactis acted synergistically with ZWF1 overexpression in the presence of glucose, but had a detrimental effect after the diauxic shift. Expression of the mitochondrial NADH kinase Pos5 in the cytosol likewise improved the production of xylitol only on glucose, but not in combination with enhanced Zwf1 activity. To demonstrate the generalizability of our observations, we show that the most promising strategies - ZWF1 overexpression and deletion of ALD6 - also improve the production of l-galactonate from d-galacturonic acid. Therefore, we expect that these findings will provide valuable guidelines for engineering not only the production of xylitol but also of diverse other pathways that require NADPH.

01 Nov 2024·Life Sciences

ALDH and cancer stem cells: Pathways, challenges, and future directions in targeted therapy

Review

Author: Kokkanti, Rekha Rani ; Wang, Qi-En ; Nuguri, Shreya Madhav ; Pandey, Prashant ; Lavudi, Kousalya

Human ALDH comprise 19 subfamilies in which ALDH1A1, ALDH1A3, ALDH3A1, ALDH5A1, ALDH7A1, and ALDH18A1 are implicated in CSC. Studies have shown that ALDH can also be involved in drug resistance and standard chemotherapy regimens are ineffective in treating patients at the stage of disease recurrence. Existing chemotherapeutic drugs eliminate the bulk of tumors but are usually not effective against CSC which express ALDH+ population. Henceforth, targeting ALDH is convincing to treat the patient's post-relapse. Combination therapies that interlink signaling mechanisms seem promising to increase the overall disease-free survival rate. Therefore, targeting ALDH through ALDH inhibitors along with immunotherapies may create a novel platform for translational research. This review aims to fill in the gap between ALDH1 family members in relation to its cell signaling mechanisms, highlighting their potential as molecular targets to sensitize recurrent tumors and bring forward the future development concerning the current progress and draw backs. This review summarizes the role of cancer stem cells and their upregulation by maintaining the tumor microenvironment in which ALDH is specifically highlighted. It discusses the regulation of ALDH family proteins and the crosstalk between ALDH and CSC in relation to cancer metabolism. Furthermore, it establishes the correlation between ALDH involved signaling mechanisms and their specific targeted inhibitors, as well as their functional modularity, bioavailability, and mechanistic role in various cancers.

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ALDH1A3

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