Work

Pathomechanisms Underlying X‐Adrenoleukodystrophy: A Three‐Hit Hypothesis

Year: 2010

Type: review

Abstract: X-adrenoleukodystrophy (X-ALD) is a complex disease where inactivation of ABCD1 gene results in clinically diverse phenotypes, the fatal disorder of cerebral ALD (cALD) or a milder disorder of adrenomyeloneuropathy (AMN). Loss of ABCD1 function results in defective beta oxidation of very long chain fatty acids (VLCFA) resulting in excessive accumulation of VLCFA, the biochemical "hall mark" of X-ALD. At present, the ABCD1-mediated mechanisms that determine the different phenotype of X-ALD are not well understood. The studies reviewed here suggest for a "three-hit hypothesis" for neuropathology of cALD. An improved understanding of the molecular mechanisms associated with these three phases of cALD disease should facilitate the development of effective pharmacological therapeutics for X-ALD.

Source: Brain Pathology

DOI: 10.1111/j.1750-3639.2010.00392.x

Authors: Inderjit Singh, Aurora Pujol

Institutions: Medical University of South Carolina, Institució Catalana de Recerca i Estudis Avançats, Institut d'Investigació Biomédica de Bellvitge, Centre for Biomedical Network Research on Rare Diseases

Language: English

Topic: Metabolism and Genetic Disorders

Subfield: Clinical Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute of Neurological Disorders and Stroke