title: DNA damage response in peripheral nervous system: coping with cancer therapy-induced DNA lesions.
abstract: In the absence of blood brain barrier (BBB) the DNA of peripheral nervous system (PNS) neurons is exposed to a broader spectrum of endogenous and exogenous threats compared to that of the central nervous system (CNS). Hence, while CNS and PNS neurons cope with many similar challenges inherent to their high oxygen consumption and vigorous metabolism, PNS neurons are also exposed to circulating toxins and inflammatory mediators due to relative permeability of PNS blood nerve barrier (BNB). Consequently, genomes of PNS neurons incur greater damage and the question awaiting investigation is whether specialized repair mechanisms for maintenance of DNA integrity have evolved to meet the additional needs of PNS neurons. Here, I review data showing how PNS neurons manage collateral DNA damage incurred in the course of different anti-cancer treatments designed to block DNA replication in proliferating tumor cells. Importantly, while PNS neurotoxicity and concomitant chemotherapy-induced peripheral neuropathy (CIPN) are among major dose limiting barriers in achieving therapy goals, CIPN is partially reversible during post-treatment nerve recovery. Clearly, cell recovery necessitates mobilization of the DNA damage response and underscores the need for systematic investigation of the scope of DNA repair capacities in the PNS to help predict post-treatment risks to recovering neurons.
authors.affiliation: Department of Surgery, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA. elenglan@utmb.edu
authors.forename: Ella W
authors.initials: EW
authors.lastname: Englander
mesh_terms: D000818:Animals; D050256:Antimitotic Agents / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001812:Blood-Brain Barrier / Q000473:pathology; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair; D004195:Disease Models, Animal; D006801:Humans; D009369:Neoplasms / Q000473:pathology / Q000628:therapy; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D017933:Peripheral Nervous System / Q000187:drug effects / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000473:pathology
chemical_list: D050256:Antimitotic Agents; D000970:Antineoplastic Agents; D004247:DNA
keywords: Base excision repair (BER); Blood brain barrier (BBB); Blood nerve barrier (BNB); Chemotherapy-induced peripheral neuropathy (CIPN); Cisplatin cross-links; Cytosine arabinoside (ara-C); Dorsal root ganglion (DRG); Ionizing radiation (IR); Nucleotide excision repair (NER); Peripheral nervous system (PNS)