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Human genetic syndromes deficient in nucleotide excision repair (NER), such as xeroderma pigmentosum and Cockayne syndrome, may present neurological abnormalities and premature aging symptoms. Unrepaired endogenously generated DNA damage that hampers transcription is a strong candidate that contributes to the development of these severe effects in neuronal tissue. Endogenous lesions include those generated due to byproducts of cellular metabolisms, such as reactive oxygen species. This review presents much of the evidence on the mechanisms related to neurodegenerative processes associated with DNA damage responses. The primary focus is on the effects of the transcription machinery, including the accumulation of DNA•RNA hybrids (R-loops) that, in turn, influence DNA damage and repair metabolism. Moreover, several neuronal tissues present higher expression of long genes, a genomic subset more affected by DNA lesions, which may explain part of the neurological abnormalities in these patients. Also, neuronal tissues have different DNA repair capabilities that might result in different neurological consequences, as observed in patients and NER deficient animal models. The better understanding of how the accumulation of transcription blocking lesions can lead to neurological abnormalities and premature aging-like phenotypes may assist us in finding potential biomarkers and therapeutic targets that might improve the lives of these patients, as well as other neurological disorders in the general population. This work was supported under the International Collaboration Research Funding from São Paulo Research Foundation (FAPESP, SP, Brazil) and the Netherlands Organization for Scientific Research – NWO (Grant #2019/19435-3). Financial support was also received from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Grant #308868/2018-8) and Coordenação de Aperfeiçoamento de Pessoal do Ensino Superior (CAPES, Brasília, DF, Brazil, financial code 001).

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Este trabalho se debruça sobre o jornal O Binóculo, que circulou em Belém no final do século XIX, a partir de 1897. Com narrativa construída em torno de personagens do demi-monde belenense, O Bínóculo tece em suas páginas uma sociedade binoquiana que circula pela urbe, problematizando questões especificas daquela sociedade, submersa nos ideais de modernidade e progresso e vivendo sob o signo da Belle- Époque. Nesse sentido, O Binóculo desenvolve íntimo dialogo com a imprensa “critica e noticiosa” da época e suas representações urbanas e sociais. Assim, só é possível compreender como este jornal se tornou possível em Belém, em fins do século XIX, se compreendermos também os signos discursivos que formavam a cidade bellepoquiana. This work leans over on the periodical O Binóculo, that circulated in Belém in the end of century XIX, from 1897. With narrative constructed around personages of demi-monde belenense, O Binóculo weaves in its pages a binoquiana society that circulates for urbe, considering questions specifies of that society, submerged in the ideals of modernity and progress and living under the sign of the Belle- Époque. In this direction, O Binóculo develops intimate dialogues with the press “criticizes and urban and social news” of the time and its representations. Therefore, it is only possible to understand as this periodical it is became possible in Belém, in ends of century XIX, if also to understand the discuss signs that formed the bellepoquiana city.