Modelling the functional genomics of Parkinson's disease in Caenorhabditis elegans: LRRK2 and beyond.
Biosci Rep
; 41(9)2021 09 30.
Article
em En
| MEDLINE
| ID: mdl-34397087
ABSTRACT
For decades, Parkinson's disease (PD) cases have been genetically categorised into familial, when caused by mutations in single genes with a clear inheritance pattern in affected families, or idiopathic, in the absence of an evident monogenic determinant. Recently, genome-wide association studies (GWAS) have revealed how common genetic variability can explain up to 36% of PD heritability and that PD manifestation is often determined by multiple variants at different genetic loci. Thus, one of the current challenges in PD research stands in modelling the complex genetic architecture of this condition and translating this into functional studies. Caenorhabditis elegans provide a profound advantage as a reductionist, economical model for PD research, with a short lifecycle, straightforward genome engineering and high conservation of PD relevant neural, cellular and molecular pathways. Functional models of PD genes utilising C. elegans show many phenotypes recapitulating pathologies observed in PD. When contrasted with mammalian in vivo and in vitro models, these are frequently validated, suggesting relevance of C. elegans in the development of novel PD functional models. This review will discuss how the nematode C. elegans PD models have contributed to the uncovering of molecular and cellular mechanisms of disease, with a focus on the genes most commonly found as causative in familial PD and risk factors in idiopathic PD. Specifically, we will examine the current knowledge on a central player in both familial and idiopathic PD, Leucine-rich repeat kinase 2 (LRRK2) and how it connects to multiple PD associated GWAS candidates and Mendelian disease-causing genes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
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Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina
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Mutação
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Neurônios
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biosci Rep
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido