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Transient oligomeric species formed during the aggregation process of the 42-residue form of the amyloid-β peptide (Aβ 42 ) are key pathogenic agents in Alzheimer’s disease (AD). To investigate the relationship between Aβ 42 aggregation and its cytotoxicity and the influence of a potential drug on both phenomena, we have studied the effects of trodusquemine. This aminosterol enhances the rate of aggregation by promoting monomer-dependent secondary nucleation, but significantly reduces the toxicity of the resulting oligomers to neuroblastoma cells by inhibiting their binding to the cellular membranes. When administered to a C. elegans model of AD, we again observe an increase in aggregate formation alongside the suppression of Aβ 42 -induced toxicity. In addition to oligomer displacement, the reduced toxicity could also point towards an increased rate of conversion of oligomers to less toxic fibrils. The ability of a small molecule to reduce the toxicity of oligomeric species represents a potential therapeutic strategy against AD.

O presente trabalho tem como objetivo uma reflexão sobre a voz como um índice da presença do sujeito na linguagem no contexto da clínica dos distúrbios de linguagem, com base no exercício clínico da Fonoaudiologia e a partir de quatro interrogantes, condutores da reflexão: 1) Uma abordagem clínica da voz que considere a linguagem é possível?; 2) Uma abordagem clínica da linguagem que considere a voz é possível?; 3) Qual é o lugar da voz na clínica dos distúrbios de linguagem?; e, por fim, 4) Qual é a relação entre o sujeito falante e o ouvinte, a partir da voz, na clínica dos distúrbios de linguagem? Na tentativa de encontrar possíveis respostas às questões, o trabalho inicia com uma revisão dos principais achados bibliográficos concernentes à concepção de voz e dos distúrbios vocais para o campo da Fonoaudiologia. Em seguida, busca-se apoio teórico na teoria da enunciação proposta pelo linguista Émile Benveniste, posto que, mesmo que esse autor não tenha se dedicado a estudar diretamente a voz ou a clínica dos distúrbios de linguagem, é possível encontrar expressões que dão indícios da presença da voz em sua obra, além de noções como enunciação, sujeito, ato enunciativo e linguagem, que também fornecem importantes reflexões sobre o tema abordado neste trabalho Por fim, dialogando com algumas das exposições de Benveniste e de outros teóricos – advindos tanto da Linguística como de outras áreas –, são expostas breves vinhetas clínicas, traçando, então, uma discussão teórico-clínica, que permite perceber que é através da voz que o sujeito falante, na singularidade do ato enunciativo, produz suas marcas na linguagem, mesmo quando a articulação da fala está ausente. A partir dessas reflexões, a voz é considerada um índice da presença do sujeito na linguagem no contexto da clínica dos distúrbios de linguagem. This study aims at a consideration of the voice as an index of the presence of the subject in language in the context of the language disorders clinic, based on the clinical exercise of Speech Therapy and on four questions: 1) Is a clinical approach to voice that considers language possible?; 2) Is a clinical approach to language that considers voice possible?; 3) What is the place of voice in the language disorders clinic?; and, finally, 4) What is the relationship between the speaking subject and the listener, based on the voice, in the language disorders clinic? Attempting to find the possible answers to these questions, the study begins with a review of the main bibliographic findings concerning the concept of voice and of vocal disorders in the field of Speech Therapy. Subsequently, theoretical support is sought in the enunciation theory proposed by linguist Émile Benveniste, since, even though this author did not directly study the voice or the language disorders clinic, it is possible to find expressions that give indications of the presence of the voice in his works, as well as notions such as enunciation, subject, enunciative act and language, which also provide important reflections about the topic of this research Finally, in dialogue with some examinations by Benveniste and by other theorists—from both Linguistics and other areas—, brief clinical vignettes are exposed, therefore establishing a theoretical-clinical discussion, enabling the perception that it is through the voice that the speaking subject, in the singularity of the enunciative act, produces their marks in language, even when the articulation of speech is absent. Based on these reflections, the voice is regarded as an index of the presence of the subject in language in the context of the language disorders clinic.

Transient oligomeric species formed during the aggregation process of the 42-residue form of the amyloid-β peptide (Aβ42) are key pathogenic agents in Alzheimer's disease (AD). To investigate the relationship between Aβ42 aggregation and its cytotoxicity and the influence of a potential drug on both phenomena, we have studied the effects of trodusquemine. This aminosterol enhances the rate of aggregation by promoting monomer-dependent secondary nucleation, but significantly reduces the toxicity of the resulting oligomers to neuroblastoma cells by inhibiting their binding to the cellular membranes. When administered to a C. elegans model of AD, we again observe an increase in aggregate formation alongside the suppression of Aβ42-induced toxicity. In addition to oligomer displacement, the reduced toxicity could also point towards an increased rate of conversion of oligomers to less toxic fibrils. The ability of a small molecule to reduce the toxicity of oligomeric species represents a potential therapeutic strategy against AD.