Peroxisomes play a major role in human cellular lipid metabolism, including fatty acid β-oxidation. The most frequent peroxisomal disorder is X-linked adrenoleukodystrophy, which is caused by mutations in ABCD1. The biochemical hallmark of X-linked adrenoleukodystrophy is the accumulation of very long chain fatty acids (VLCFAs) due to impaired peroxisomal β-oxidation. Although this suggests a r...

The rhizomelic form of chondrodysplasia punctata (RCDP) is a peroxisomal disorder characterized biochemically by an impairment of plasmalogen biosynthesis and phytanate catabolism. We have now found that the maturation of peroxisomal 3-oxoacyl-CoA thiolase is impaired in fibroblasts from RCDP patients. To establish the subcellular localization of the 3-oxoacylCoA thiolase precursor protein, cul...

Two peroxisome targeting signals (PTSs) for matrix proteins have been well defined to date. PTS1 comprises a COOH-terminal tripeptide, SKL, and has been found in several matrix proteins, whereas PTS2 has been found only in peroxisomal thiolase and is contained within an NH2-terminal cleavable presequence. We have investigated the functional integrity of the import routes for PTS1 and PTS2 in fi...

Rhizomelic chondrodysplasia punctata is a human autosomal recessive disorder characterized by skeletal, eye and brain abnormalities. The disorder is caused by mutations in the PEX7 gene, which encodes the receptor for a class of peroxisomal matrix enzymes. We describe the generation and characterization of a Pex7 mouse knockout (Pex7(-/-)). Pex7(-/-) mice are born severely hypotonic and have a ...

Zellweger syndrome, a paradigm of human peroxisomal disorders is characterized by dysmorphic features, hypotonia, severe neuro-developmental delay, hepatomegaly, renal cysts, sensorineural deafness and retinal dysfunction. This is a case report of a baby boy born with facial dysmorphism, profound hypotonia, seizures, and hepatomegaly. The diagnosis was not evident initially but only later when ...

Alzheimer’s disease (AD) is a complex cognitive disorder for which the single greatest risk factor is age. The pathophysiological basis for AD is still a matter of debate with no current hypothesis explaining all of the complex pathological changes observed. These include neurofibrillary tangles, amyloid plaques, neuroinflammation, hypomyelination, neuronal shrinkage (eg. Nbasalis cholinergic n...

Several patients have been described recently who suffer from a non-rhizomelic type of chondrodysplasia punctata (CDP), but who show all the biochemical abnormalities characteristic of the rhizomelic form of chondrodysplasia punctata (RCDP), a peroxisomal disorder. We have used protease protection experiments and microinjection of repotter-protein-encoding expression plasmids to show that perox...

AN adult onset novel disorder of peroxisomal function is described, characterised by retinitis pigmentosa resulting in progressive visual failure, learning difficulties, a peripheral neuropathy, and hypogonadism. The defect results in accumulation of pristanic acid, and the bile acid intermediates, dihydroxycholestanoic and trihydroxycholestanoic acid, and is due to a deficiency of alpha-methyl...