Related Experiment Video
Updated: Mar 28, 2026
Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents
Published on: August 10, 2018
Novel Therapeutic Targets and Drug Candidates for Modifying Disease Progression in Adrenoleukodystrophy
1Laboratory of Neurometabolic Diseases and Pathologic Anatomy Service, Institute of Neuropathology, Bellvitge Biomedical Research Institute (IDIBELL)-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat and Center for Biomedical Research on Rare Diseases (CIBERER), U759, ISCIII, and Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain.
Abstract:
X-linked adrenoleukodystrophy (X-ALD) is the most frequent inherited monogenic demyelinating disease. It is often lethal and currently lacks a satisfactory therapy. The disease is caused by loss of function of the ABCD1 gene, a peroxisomal ATP-binding cassette transporter, resulting in the accumulation of very-long-chain fatty acids (VLCFA) in organs and plasma. Recent findings on pathomechanisms of the peroxisomal neurometabolic disease X-ALD have provided important clues on therapeutic targets. Here we describe the impact of chronic redox imbalance caused by the excess VLCFA on mitochondrial biogenesis and respiration, and explore the consequences on the protein quality control systems essential for cell survival, such as the proteasome and autophagic flux. Defective proteostasis, together with mitochondrial malfunction, is a hallmark of the most prevalent neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and of the aging process. Thus, we discuss molecular targets and emerging treatment options that may be common to both multifactorial neurodegenerative disorders and X-ALD. New-generation antioxidants, some of them mitochondrial targeted, mitochondrial biogenesis boosters such as pioglitazone and resveratrol, and the mTOR inhibitor temsirolimus hold promise as disease-modifying therapies.
Insights
X-linked adrenoleukodystrophy (X-ALD) stems from ABCD1 gene dysfunction, leading to toxic very-long-chain fatty acid buildup. Therapies targeting redox imbalance and mitochondrial health show promise for X-ALD and other neurodegenerative diseases.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- X-linked adrenoleukodystrophy (X-ALD) is a severe inherited demyelinating disease with no effective treatments.
- It arises from ABCD1 gene mutations, causing toxic very-long-chain fatty acid (VLCFA) accumulation.
- Understanding X-ALD's mechanisms offers insights into broader neurodegenerative disorders.
Purpose of the Study:
- To investigate the impact of VLCFA-induced redox imbalance on mitochondrial function in X-ALD.
- To explore the effects on cellular protein quality control systems (proteostasis).
- To identify potential therapeutic targets common to X-ALD and other neurodegenerative diseases.
Main Methods:
- Analysis of redox imbalance and its effects on mitochondrial biogenesis and respiration.
- Assessment of proteasome and autophagic flux in response to VLCFA accumulation.
- Review of emerging therapeutic strategies for X-ALD and related conditions.
Main Results:
- Excess VLCFA causes chronic redox imbalance, impairing mitochondrial function.
- Defective proteostasis and mitochondrial malfunction are key features of X-ALD.
- These cellular defects are shared with neurodegenerative diseases like Alzheimer's and Parkinson's.
Conclusions:
- Mitochondrial dysfunction and impaired proteostasis are central to X-ALD pathogenesis.
- Targeting these pathways, alongside redox balance, offers potential disease-modifying therapies.
- Emerging treatments like antioxidants, mitochondrial boosters, and mTOR inhibitors show promise for X-ALD.
More Related Videos
04:45Lumbar Intrathecal Injection of SOD1-ASOs for Precise CNS Targeting and Predictive Efficacy in Human SOD1-G93A ALS Mice
Published on: February 24, 2026
11:44Cellular Membrane Affinity Chromatography Columns to Identify Specialized Plant Metabolites Interacting with Immobilized Tropomyosin Kinase Receptor B
Published on: January 19, 2022
Related Concept Videos
01:22Alzheimer's Disease: Treatment
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
01:26Targets for Drug Action: Overview
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
01:29Drugs Affecting Neurotransmitter Synthesis
01:29Pharmacogenomics: Identification of New Drug Targets
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...