Xeroderma Pigmentosum: Overview of Pharmacology and Novel Therapeutic Strategies for Neurological Symptoms

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2018 Dec 1

PMID 30499105

Citations 18

Authors

Rosella Abeti

Anna Zeitlberger

Colm Peelo

Hiva Fassihi

Robert P E Sarkany

Alan R Lehmann

Paola Giunti

Affiliations

Soon will be listed here.

Abstract

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.

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