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Publication
Genes envolvidos na determinaĆ§Ć£o de Parkinson
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|---|---|---|---|---|
| PPG_26118 | 979.79 KB | Adobe PDF |
Advisor(s)
Abstract(s)
A doenƧa de Parkinson Ć© a segunda doenƧa neurodegenerativa com maior expressĆ£o na
atualidade, afetando cerca de 3% dos indivĆduos com mais de 80 anos. Os sintomas
clĆnicos desta doenƧa sĆ£o tremor em repouso, instabilidade postural, bradicinesia e
rigidez, com boa resposta ao tratamento com levodopa.
Nos Ćŗltimos anos desenvolveram-se vĆ”rios estudos que tornaram inquestionĆ”vel a
contribuiĆ§Ć£o de fatores genĆ©ticos para a complexa patogĆ©nese desta doenƧa. Foram
descobertas mutaƧƵes altamente penetrantes capazes de produzir formas monogƩnicas
raras da doenƧa de Parkinson em genes como o SNCA, Parkina, DJ-1, PINK 1, LRRK2
e VPS35. Variantes Ćŗnicas, com penetrĆ¢ncias incompletas dos genes LRRK2 e GBA,
apresentam-se como fatores de risco para a doenƧa em determinadas populaƧƵes. AlƩm
disso, mais de vinte variantes comuns, que produzem efeitos de pequenas dimensƵes, sĆ£o
tidas como responsĆ”veis pela modelaĆ§Ć£o do risco para a doenƧa de Parkinson.
A investigaĆ§Ć£o de formas Mendelianas da doenƧa de Parkinson permitiu um
conhecimento privilegiado sobre a fisiopatologia por detrƔs das formas idiopƔticas mais
comuns da doenƧa.
Apesar de todos os avanƧos no campo da genĆ©tica, este tipo de investigaĆ§Ć£o ainda nĆ£o
contribuiu para o surgimento de novas terapĆŖuticas sendo que este Ć© o principal interesse
da sua investigaĆ§Ć£o futura. O desafio, na prĆ³xima dĆ©cada, serĆ” procurar dados que
fortaleƧam as informaƧƵes jĆ” existentes em relaĆ§Ć£o Ć genĆ©tica da doenƧa de Parkinson,
atravĆ©s do conhecimento das consequĆŖncias biolĆ³gicas das variantes de risco. AlĆ©m disso,
tambĆ©m se espera que os estudos de associaĆ§Ć£o genĆ³mica e a implementaĆ§Ć£o de novas
tecnologias de investigaĆ§Ć£o como a ānext generation sequencingā e a sequenciaĆ§Ć£o do
exoma sejam uma ajuda valiosa na identificaĆ§Ć£o de novas variantes de risco da forma
esporƔdica da doenƧa de Parkinson.
Parkinsonās disease is the secound most important neurodegenerative disorder, affecting 3% of those older than 80 years of age. The clinical symptoms are resting tremor, postural instability, bradykinesia and rigidity, with a good response to levodopa therapy. Over the last years, numerous studies have confirmed the unquestionable contribution of genetic factos to the complex pathogenesis of this disease. Highly penetrant mutations producing rare, monogenic forms of the disease have been discovered in singular genes such as SNCA, Parkin, DJ-1, PINK 1, LRRK2, and VPS35. Unique variants with incomplete penetrance in LRRK2 and GBA have been shown to be strong risk factors for Parkinsonās disease in certain populations. Additionally, over 20 common variants with small effect sizes are now recognized to modulate the risk for Parkinsonās disease. Investigating Mendelian forms of PD has provided precious insight into the pathophysiology that underlies the more common idiopathic form of disease. Despite all the advances on the genetic field, no treatment methodologies have been developed. The challenge over the next decade will be to strengthen the findings delivered through genetic discovery by assessing the direct, biological consequences of risk variants. Moreover, i salso expected that the advent of genome-wide association studies and the implementation of new technologies, like next generation sequencing and exome sequencing has undoubtedly greatly aided the identification on novel risk variants for sporadic Parkinsonās Disease.
Parkinsonās disease is the secound most important neurodegenerative disorder, affecting 3% of those older than 80 years of age. The clinical symptoms are resting tremor, postural instability, bradykinesia and rigidity, with a good response to levodopa therapy. Over the last years, numerous studies have confirmed the unquestionable contribution of genetic factos to the complex pathogenesis of this disease. Highly penetrant mutations producing rare, monogenic forms of the disease have been discovered in singular genes such as SNCA, Parkin, DJ-1, PINK 1, LRRK2, and VPS35. Unique variants with incomplete penetrance in LRRK2 and GBA have been shown to be strong risk factors for Parkinsonās disease in certain populations. Additionally, over 20 common variants with small effect sizes are now recognized to modulate the risk for Parkinsonās disease. Investigating Mendelian forms of PD has provided precious insight into the pathophysiology that underlies the more common idiopathic form of disease. Despite all the advances on the genetic field, no treatment methodologies have been developed. The challenge over the next decade will be to strengthen the findings delivered through genetic discovery by assessing the direct, biological consequences of risk variants. Moreover, i salso expected that the advent of genome-wide association studies and the implementation of new technologies, like next generation sequencing and exome sequencing has undoubtedly greatly aided the identification on novel risk variants for sporadic Parkinsonās Disease.
Description
Keywords
DoenƧa de Parkinson GenĆ©tica Alelos de risco Tratamento farmacolĆ³gico Parkinsonās disease Genetics Risk alleles Pharmacological treatment