Loading...
Publication
Doença de Machado-Joseph : abordagem terapêutica e de terapia génica
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 1.3 MB | Adobe PDF |
Advisor(s)
Abstract(s)
A doença de MachadoJoseph (DMJ) ou ataxia espinocerebelar 3 (SCA3), é uma doença neurodegenerativa, pertencente ao grupo das doenças de poliglutamina (poliQ). Molecularmente é causada pela expansão de uma repetição CAG na região codificante do gene ATXN3.
Esta é a ataxia mais comum herdada de forma dominante. Relativamente a Portugal, este é um país com elevada prevalência desta doença. No continente representam 56 % de todas as ataxias AD, correspondendo a uma prevalência de 3,1/100000 habitantes, e de 41,6/1000000 habitantes na região dos Açores.
Carateriza-se pelo seu aparecimento tardio, entre os 35 e os 40 anos, e pela perda
progressiva das funções motoras, levando à morte.
Apesar da causa monogénica da doença, a sua fisiopatologia permanece indefinida. A mutação resulta numa proteína dobrada de forma atípica que agrega e afeta várias funções celulares, incluindo a transcrição do RNA, a homeostase da proteína e a transmissão sináptica.
Atualmente, não há cura para a DMJ, no entanto, a crescente compreensão da patogénese da doença oferece diferentes caminhos para potenciais terapêuticas.
Esta dissertação tem como objetivo realizar uma revisão narrativa sobre a abordagem terapêutica e terapia genética na Doença de MachadoJoseph (DMJ).
Numerosos estudos têm-se focado no desenvolvimento de tratamentos que visam a doença em diferentes estágios, prevenindo a agregação de proteínas, aumentando a depuração de proteínas mutantes e combatendo os mecanismos de disfunção celular. Nos últimos anos, também tem havido um foco crescente no desenvolvimento de terapias genéticas, sugerindo que, no futuro, essa doença debilitante possa ser prevenida.
MachadoJoseph disease (MJD) or spinocerebellar ataxia 3 (SCA3) is a neurodegenerative disease belonging to the group of polyglutamine (polyQ) diseases. Molecularly CA G is the expansion of a coding region of the ATXN3 gene. This is the most common dominantly inherited ataxia. Regarding Portugal, this is a country with prevalence of this disease. On the mainland 56% of all AD ataxias, corresponding to a prevalence of 3.1/100000 inhabitants, and 41.6/1000000 inhabitants in the Azores region. It is characterized by its onset and delay, between the ages of 35 and 40 years, and by the loss of motor functions, leading to death. Despite the monogenic cause of the disease, its pathophysiology remains unclear. A folded form of protein is a form of protein that aggregates several cellular functions, including a protein that aggregates several RNA functions. Currently, there is no cure for MJD, however, understanding the pathogenesis of the disease offers different avenues for therapeutics. This dissertation aims to review the therapeutic approach and gene therapy in MachadoJoseph Disease (MJD). Numerous studies have focused on the development of treatment studies that target a disease in different methods, preventing the action of proteins, increasing the clearance of mutant proteins and combating the mechanisms of cellular dysfunction. In recent years, it has also prevented an increasing focus on the development of gene therapies, suggesting that in the future this debilitating disease could be harnessed.
MachadoJoseph disease (MJD) or spinocerebellar ataxia 3 (SCA3) is a neurodegenerative disease belonging to the group of polyglutamine (polyQ) diseases. Molecularly CA G is the expansion of a coding region of the ATXN3 gene. This is the most common dominantly inherited ataxia. Regarding Portugal, this is a country with prevalence of this disease. On the mainland 56% of all AD ataxias, corresponding to a prevalence of 3.1/100000 inhabitants, and 41.6/1000000 inhabitants in the Azores region. It is characterized by its onset and delay, between the ages of 35 and 40 years, and by the loss of motor functions, leading to death. Despite the monogenic cause of the disease, its pathophysiology remains unclear. A folded form of protein is a form of protein that aggregates several cellular functions, including a protein that aggregates several RNA functions. Currently, there is no cure for MJD, however, understanding the pathogenesis of the disease offers different avenues for therapeutics. This dissertation aims to review the therapeutic approach and gene therapy in MachadoJoseph Disease (MJD). Numerous studies have focused on the development of treatment studies that target a disease in different methods, preventing the action of proteins, increasing the clearance of mutant proteins and combating the mechanisms of cellular dysfunction. In recent years, it has also prevented an increasing focus on the development of gene therapies, suggesting that in the future this debilitating disease could be harnessed.
Description
Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas Moniz
Keywords
Doença de Machado-Joseph Ataxia espinocerebelosa tipo 3 Diagnóstico Terapia genética