Xeroderma pigmentosum: overview of pharmacology and novel therapeutic strategies for neurological symptoms.

Autor: Abeti R; Ataxia Centre, Department of Clinical and Movement Neurosciences, University College London, Institute of Neurology London, London, UK., Zeitlberger A; Ataxia Centre, Department of Clinical and Movement Neurosciences, University College London, Institute of Neurology London, London, UK., Peelo C; Ataxia Centre, Department of Clinical and Movement Neurosciences, University College London, Institute of Neurology London, London, UK., Fassihi H; National Xeroderma Pigmentosum Service, St John's Institute of Dermatology Guy's and St Thomas' Foundation Trust, London, UK., Sarkany RPE; National Xeroderma Pigmentosum Service, St John's Institute of Dermatology Guy's and St Thomas' Foundation Trust, London, UK., Lehmann AR; Genome Damage and Stability Centre, University of Sussex, Brighton, UK., Giunti P; Ataxia Centre, Department of Clinical and Movement Neurosciences, University College London, Institute of Neurology London, London, UK.; National Xeroderma Pigmentosum Service, St John's Institute of Dermatology Guy's and St Thomas' Foundation Trust, London, UK.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2019 Nov; Vol. 176 (22), pp. 4293-4301. Date of Electronic Publication: 2019 Jan 23.
DOI: 10.1111/bph.14557
Abstrakt: Xeroderma pigmentosum (XP) encompasses a group of rare diseases characterized in most cases by malfunction of nucleotide excision repair (NER), which results in an increased sensitivity to UV radiation in affected individuals. Approximately 25-30% of XP patients present with neurological symptoms, such as sensorineural deafness, mental deterioration and ataxia. Although it is known that dysfunctional DNA repair is the primary pathogenesis in XP, growing evidence suggests that mitochondrial pathophysiology may also occur. This appears to be secondary to dysfunctional NER but may contribute to the neurodegenerative process in these patients. The available pharmacological treatments in XP mostly target the dermal manifestations of the disease. In the present review, we outline how current understanding of the pathophysiology of XP could be used to develop novel therapies to counteract the neurological symptoms. Moreover, the coexistence of cancer and neurodegeneration present in XP led us to focus on possible new avenues targeting mitochondrial pathophysiology. LINKED ARTICLES: This article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for Therapy Translation. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.22/issuetoc.
(© 2018 The British Pharmacological Society.)
Databáze: MEDLINE
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