Endoplasmic reticulum stress signaling in patients with X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder with a prevalence of approximately 1 in 17.000 live births. Mutations in the ABCD1 gene that encodes ALDP, an ATP-bindingcassette (ABC) transporter located in the peroxisomal membrane, results in impaired peroxisomal beta-oxidation and the subsequent accumulation of very-long-chain fatty acids (VLCFA; ≥ 22 or more carbon atoms) in plasma and tissues. Of all male patients, 35% will develop childhood cerebral adrenoleukodystrophy (CCALD), a rapidly progressive demyelinating disease of the central nervous system between 3 and 10 years of age. Most X-ALD patients develop adrenomyeloneuropathy (AMN) between the third and fourth decade of life. AMN is characterized by slow progressive stiffness and weakness of the legs, impaired vibration sense in the lower limbs, spincter disturbance and impotence, commonly associated wth primary adrenocortical and/or testicular insufficiency. At present, more than 500 mutations in the ABCD1 gene have been identified but no genotype-fenotype correlation is observed. We tested if VLCFA induce endoplasmic reticulum stress signaling in cultured cell lines from X-ALD patients. …