Rare Diseases Symptoms Automatic Extraction

Antioxidants halt axonal degeneration in a mouse model of X-adrenoleukodystrophy.

[adrenomyeloneuropathy]

Axonal degeneration is a main contributor to disability in progressive neurodegenerative diseases in which oxidative stress is often identified as a pathogenic factor. We aim to demonstrate that antioxidants are able to improve axonal degeneration and locomotor deficits in a mouse model of X-adrenoleukodystrophy (X-ALD).X-ALD is a lethal disease caused by loss of function of the ABCD1 peroxisomal transporter of very long chain fatty acids (VLCFA). The mouse model for X-ALD exhibits a late onset neurological phenotype with locomotor disability and axonal degeneration in spinal cord resembling the most common phenotype of the disease, adrenomyeloneuropathy (X-AMN). Recently, we identified oxidative damage as an early event in life, and the excess of VLCFA as a generator of radical oxygen species (ROS) and oxidative damage to proteins in X-ALD.Here, we prove the capability of the antioxidants N-acetyl-cysteine, α-lipoic acid, and α-tocopherol to scavenge VLCFA-dependent ROS generation in vitro. Furthermore, in a preclinical setting, the cocktail of the 3 compounds reversed: (1) oxidative stress and lesions to proteins, (2) immunohistological signs of axonal degeneration, and (3) locomotor impairment in bar cross and treadmill tests.We have established a direct link between oxidative stress and axonal damage in a mouse model of neurodegenerative disease. This conceptual proof of oxidative stress as a major disease-driving factor in X-AMN warrants translation into clinical trials for X-AMN, and invites assessment of antioxidant strategies in axonopathies in which oxidative damage might be a contributing factor.

Diseases presenting "and" symptom

  • achondroplasia
  • adrenomyeloneuropathy
  • aniridia
  • carcinoma of the gallbladder
  • cutaneous mastocytosis
  • cystinuria
  • esophageal squamous cell carcinoma
  • harlequin ichthyosis
  • hodgkin lymphoma, classical
  • hydrocephalus with stenosis of the aqueduct of sylvius
  • kallmann syndrome
  • liposarcoma
  • locked-in syndrome
  • neonatal adrenoleukodystrophy
  • omenn syndrome
  • oral submucous fibrosis
  • pleomorphic liposarcoma
  • primary hyperoxaluria type 1
  • proteus syndrome
  • pyomyositis
  • pyruvate dehydrogenase deficiency
  • sneddon syndrome
  • triple a syndrome
  • trochlear dysplasia

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