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Neurological Disorders and Challenging Intervention in Xeroderma Pigmentosum and Cockayne Syndrome

  • Masaharu HayashiEmail author
Chapter

Abstract

Xeroderma pigmentosum (XP) is a genetic disorder in DNA nucleotide excision repair and is characterized by skin disorders and progressive neurological impairment, which is complicated in some complementation groups, especially in XP group A (XP-A). Cockayne syndrome (CS) is caused by abnormalities in genes of transcription-coupled repair, and patients with CS develop growth failure, characteristic facial features, skin symptoms, and neurological disorders. Model animals have not reproduced neurological disorders in either XP-A or CS. We have performed immunohistochemistry for oxidative stress markers, antioxidant enzymes, neurotransmitters, and markers of glial cells in autopsy brains. We have also performed enzyme-linked immunosorbent assay for oxidative stress in the urines and cerebrospinal fluid, isolated from patients with XP-A and CS. It has been demonstrated that oxidative DNA damage, disturbed metabolism of monoamines and melatonin, vascular changes in the brain, and/or pathology of oligodendrocytes and microglial cells may be involved in neurodegeneration, suggesting the possibility of treatments with free radical scavengers, monoaminergic agents, and/or melatonin. We reported that the therapy with low dose of levodopa ameliorated laryngeal dystonia and involuntary movements in the arm in some patients with XP-A. In addition, it is speculated that melatonin may be a therapeutic option in patients with XP-A and CS.

Keywords

Xeroderma pigmentosum Cockayne syndrome Immunohistochemistry Enzyme-linked immunosorbent assay Oxidative stress Monoamine Melatonin Glial cells 

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Brain Development and Neural RegenerationTokyo Metropolitan Institute of Medical ScienceTokyoJapan

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