Related Experiment Video
Updated: Oct 1, 2025
07:25
Author Spotlight: A Focus on Standardized Salivary Gland Ultrasound Protocol in Connective Tissue Disease Research
Published on: October 13, 2023
3.3K
Sjögren-Larsson syndrome: A biochemical rationale for using aldehyde-reactive therapeutic agents
William B Rizzo1,2, Dana S'aulis2, Elizabeth Dorwart2
1Child Health Research Institute, Omaha, NE, USA.
Molecular Genetics and Metabolism Reports
|March 4, 2022
Summary
Sjögren-Larsson syndrome (SLS) is a neurocutaneous disease. ADX-102, an aldehyde trapping agent, protected cells from fatty aldehyde toxicity and reduced harmful N-alkyl-PE (NAPE) accumulation, suggesting therapeutic potential for SLS.
Area of Science:
- Biochemistry
- Genetics
- Cell Biology
Background:
- Sjögren-Larsson syndrome (SLS) is a rare neurocutaneous disorder.
- It stems from mutations in ALDH3A2, impairing fatty aldehyde dehydrogenase (FALDH) activity.
- This leads to the accumulation of toxic fatty aldehydes and related compounds.
Purpose of the Study:
- To investigate the therapeutic potential of ADX-102, an aldehyde trapping agent.
- To assess ADX-102's ability to mitigate fatty aldehyde toxicity in a cellular model of SLS.
- To examine ADX-102's effect on N-alkyl-PE (NAPE) formation.
Main Methods:
- Utilized Faldh-deficient Chinese hamster ovary cells (FAA-K1A) as an SLS cellular model.
- Treated FAA-K1A cells with octadecanal (C18:0-al) and ADX-102.
- Assessed cytotoxicity, apoptosis, fatty aldehyde metabolism, and NAPE levels.
Main Results:
- ADX-102 protected FAA-K1A cells from octadecanal-induced cytotoxicity and apoptosis.
- ADX-102 inhibited the metabolism of fatty aldehydes to fatty alcohols.
- ADX-102 treatment normalized the accumulation of N-alkyl-PE (NAPE) in FAA-K1A cells.
Conclusions:
- ADX-102 demonstrates efficacy in mitigating key pathological features of SLS in a cellular model.
- ADX-102 prevents the formation of toxic aldehyde adducts and inhibits detrimental metabolic pathways.
- Aldehyde-trapping molecules like ADX-102 represent a promising therapeutic strategy for Sjögren-Larsson syndrome.
Keywords:
ADX-102ADX-102, [2-(3-amino-6-chloro-quinolin-2-yl)-propan-2-ol]Aldehyde adductC16:0-al, hexadecanalC16:1-al, 2-hexadecenalC18:0-al, octadecanalCHO, Chinese hamster ovaryFALDH, fatty aldehyde dehydrogenaseFatty alcoholFatty aldehydeMetabolismN-16:0-PE, N-hexadecanyl-phosphatidylethanolamineN-18:0-PE, N-octadecanyl-phosphatidylethanolamineNAE, N-alkyl-ethanolamineNAPE, N-alkyl-phosphatidylethanolaminePE, phosphatidylethanolamineSLS, Sjögren-Larsson syndrome.
Related Concept Videos
01:18Preparation of Aldehydes and Ketones from Carboxylic Acid Derivatives
2.8K
Aldehydes are more reactive than carboxylic acids and hence, can get over-reduced to alcohol in the presence of strong reducing agents. Therefore, carboxylic acids are inefficient in preparing aldehydes using LAH.
Carboxylic acid derivatives like acid chlorides and esters are more easily reducible than the corresponding acids. The derivatives reduce in the presence of mild reducing agents to give aldehydes. Aldehydes can also be prepared by Rosenmund reduction, that is, the reduction of...
Carboxylic acid derivatives like acid chlorides and esters are more easily reducible than the corresponding acids. The derivatives reduce in the presence of mild reducing agents to give aldehydes. Aldehydes can also be prepared by Rosenmund reduction, that is, the reduction of...
2.8K
01:15Oxidations of Aldehydes and Ketones to Carboxylic Acids
4.4K
Oxidation of aldehydes and ketones results in the formation of carboxylic acids. Aldehydes, bearing hydrogen next to the carbonyl group, are easily oxidized compared to ketones. This is because an aldehydic proton can easily be abstracted during oxidation.
Aldehydes readily undergo oxidation in strong oxidizing agents such as potassium permanganate and chromic acid. The oxidation can also be carried out using mild oxidizing agents such as silver oxide. In fact, aldehydes can be easily oxidized...
Aldehydes readily undergo oxidation in strong oxidizing agents such as potassium permanganate and chromic acid. The oxidation can also be carried out using mild oxidizing agents such as silver oxide. In fact, aldehydes can be easily oxidized...
4.4K
02:37Oxidation of Alcohols
13.8K
In this lesson, the oxidation of alcohols is discussed in depth. The various reagents used for oxidation of primary and secondary alcohols are detailed, and their mechanism of action is provided.
The process of oxidation in a chemical reaction is observed in any of the three forms:
The process of oxidation in a chemical reaction is observed in any of the three forms:
13.8K
01:20Myasthenia Gravis: Overview and Treatment
2.1K
Myasthenia gravis is a neuromuscular transmission disorder characterized by weakness and increased fatigability of skeletal muscles. It is an autoimmune disease affecting approximately one in 2000 people, where antibodies against the α1 subunit of nicotinic acetylcholine receptors are produced.
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which...
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which...
2.1K
01:24Acetals and Thioacetals as Protecting Groups for Aldehydes and Ketones
4.7K
Acetals are formed by reacting two equivalents of alcohol with carbonyl compounds like aldehydes or ketones. Acetals are unaffected by bases, nucleophiles, oxidizing agents, and reducing agents. They serve as protecting groups for aldehydes and ketones. Acetals can be easily formed and also easily removed via mild acid hydrolysis.
In the presence of multiple functional groups, when selective reduction of one group over the other is desired, groups like aldehydes and ketones that form acetals...
In the presence of multiple functional groups, when selective reduction of one group over the other is desired, groups like aldehydes and ketones that form acetals...
4.7K
01:11Direct-Acting Cholinergic Agonists: Therapeutic Uses
1.1K
Direct-acting cholinergic agonists have many therapeutic uses in various medical fields. Choline esters, including acetylcholine, have limited clinical utility due to their non-selectivity and short duration of action. Still, acetylcholine and carbachol are applied topically during ophthalmologic surgery to induce miosis. Pilocarpine, a muscarinic and ganglionic stimulator, effectively treats open-angle glaucoma and alleviates xerostomia and dry mouth caused by radiotherapy or Sjögren...
1.1K