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Níveis de expressão da humanina na doença de Machado-Joseph: um estudo em amostras de sangue periférico
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Abstract(s)
A doença Machado-Joseph (DMJ) ou ataxia espinocerebelosa do tipo 3 (SCA3), é uma doença neurodegenerativa autossómica dominante que afeta o sistema nervoso central, particularmente o cerebelo. A DMJ é causada por um número anormalmente elevado de repetições CAG no gene ATXN3, o que leva à produção da proteína ataxina-3 mutada. A proteína mutada está envolvida várias vias incluindo a via mitocondrial e a apoptótica, cujas alterações estão associadas à neurodegeneração característica da doença. A DMJ é caraterizada por ataxia progressiva, espasticidade, disfagia e disartria entre outros, estando implicados na doença os sistemas, cerebeloso, piramidal, extrapiramidal, neurónio motor e oculomotor. A Humanina (HN) é um micropeptídeo traduzido a partir de um pequeno gene localizado dentro do gene RNA ribossomal 16S (MT-RNR2) no DNA mitocondrial (mtDNA). Desde a sua descoberta, a HN tem sido estudada, pela sua atividade neuroprotetora sabendo-se que está envolvida na regulação da apoptose e proteção celular contra o stress oxidativo. Existem estudos que indicam que os níveis da HN se encontram alterados em várias doenças neurodegenerativas. No entanto, dado que até ao momento, não há estudos que abordem a relação entre a HN e a DMJ, os principais objetivos do presente estudo foram: i) implementar uma metodologia laboratorial para analisar os níveis dos transcritos da HN em amostras de sangue total de doentes DMJ; ii) comparar os níveis de expressão da HN entre doentes DMJ e indivíduos saudáveis (controlos) emparelhados por idade; e iii) analisar a correlação entre os níveis de expressão da HN e os dados demográficos, clínicos e genéticos de doentes DMJ.
ABSTRACT: Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder that affects the central nervous system, particularly the cerebellum. MJD is caused by an abnormally high number of CAG repeats in the ATXN3 gene, which results in the production of the mutated ataxin-3 protein. This mutant protein is involved in several pathways including the mitochondrial and apoptotic pathways, alterations in which are associated with the neurodegeneration characteristic of the disease. MJD is characterized by progressive ataxia, spasticity, dysphagia, among others, with the cerebellar, pyramidal, extrapyramidal, motor neuron, and oculomotor systems implicated in the disease. Humanin (HN) is a micropeptide translated from a small gene located within the 16S ribosomal RNA gene (MT-RNR2) in mitochondrial DNA (mtDNA). Since its discovery, HN has been studied for its neuroprotective activity and involvement in the regulation of apoptosis and cellular protection against oxidative stress. Studies indicate HN levels are deregulated in neurodegenerative diseases. However, given that to date there are no published studies addressing the relationship between HN and MJD, the principal aims of the present study are: i) to implement a laboratory methodology for analyzing the levels of HN transcripts in whole blood samples from MJD patients; ii) to compare the HN expression levels between MJD patients and age-matched controls; and iii) to analyze the correlation between HN expression levels and demographic, clinical and genetic data in MJD patients.
ABSTRACT: Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder that affects the central nervous system, particularly the cerebellum. MJD is caused by an abnormally high number of CAG repeats in the ATXN3 gene, which results in the production of the mutated ataxin-3 protein. This mutant protein is involved in several pathways including the mitochondrial and apoptotic pathways, alterations in which are associated with the neurodegeneration characteristic of the disease. MJD is characterized by progressive ataxia, spasticity, dysphagia, among others, with the cerebellar, pyramidal, extrapyramidal, motor neuron, and oculomotor systems implicated in the disease. Humanin (HN) is a micropeptide translated from a small gene located within the 16S ribosomal RNA gene (MT-RNR2) in mitochondrial DNA (mtDNA). Since its discovery, HN has been studied for its neuroprotective activity and involvement in the regulation of apoptosis and cellular protection against oxidative stress. Studies indicate HN levels are deregulated in neurodegenerative diseases. However, given that to date there are no published studies addressing the relationship between HN and MJD, the principal aims of the present study are: i) to implement a laboratory methodology for analyzing the levels of HN transcripts in whole blood samples from MJD patients; ii) to compare the HN expression levels between MJD patients and age-matched controls; and iii) to analyze the correlation between HN expression levels and demographic, clinical and genetic data in MJD patients.
Description
Dissertação de Mestrado, Ciências Biomédicas, 28 de fevereiro de 2025, Universidade dos Açores.
Keywords
Humanina HN DMJ ATXN3 Ataxia Espinocerebelosa tipo 3 Neurodegenerativa Sangue Total Metodologia Laboratorial Transcritos qPCR
Citation
Medeiros, Fátima de Jesus Costa. (2024). "Níveis de expressão da humanina na doença de Machado-Joseph: um estudo em amostras de sangue periférico". 49 p. (Dissertação de Mestrado em Ciências Biomédicas). Ponta Delgada: Universidade dos Açores, 2024. Disponível em http://hdl.handle.net/10400.3/8640