RESUMO
The Leucine-rich repeat kinase 2 (LRRK2) gene has been identified as a disease susceptibility gene for Parkinson's disease (PD), with G2019 (6055G>A) being the most frequent mutation. This mutation was present in 42% (38/91) of Tunisian families and 2% (1/39) of US families we have studied. A founding haplotype was identified in our data and it is shared by families from Tunisia, US, European and Middle Eastern countries. The most recent common founder of the mutation was dated to 2600 (95% CI: 1950-3850) years ago although additional studies are warranted to ensure an accurate age estimate for this mutation.
Assuntos
Efeito Fundador , Haplótipos , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Idoso , Europa (Continente) , Feminino , Genótipo , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Oriente Médio , Mutação , Polimorfismo de Nucleotídeo Único , Tunísia , Estados UnidosRESUMO
Fibroblast growth factor-8 (FGF-8) is an important signaling molecule in the generation and patterning of the midbrain, tooth, and limb. In this study we show that it is also involved in eye development. In the chick, Fgf-8 transcripts first appear in the distal optic vesicle when it contacts the head ectoderm. Subsequently Fgf-8 expression increases and becomes localized to the central area of the presumptive neural retina (NR) only. Application of FGF-8 has two main effects on the eye. First, it converts presumptive retinal pigment epithelium (RPE) into NR. This is apparent by the failure to express Bmp-7 and Mitf (a marker gene for the RPE) in the outer layer of the optic cup, coupled with the induction of NR genes, such as Rx, Sgx-1 and Fgf-8 itself. The induced retina displays the typical multilayered cytoarchitecture and expresses late neuronal differentiation markers such as synaptotagmin and islet-1. The second effect of FGF-8 exposure is the induction of both lens formation and lens fiber differentiation. This is apparent by the expression of a lens specific marker, L-Maf, and by morphological changes of lens cells. These results suggest that FGF-8 plays a role in the initiation and differentiation of neural retina and lens.
Assuntos
Proteínas Aviárias , Proteínas do Olho , Olho/embriologia , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Fator de Crescimento Transformador beta , Animais , Proteína Morfogenética Óssea 7 , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular/genética , Embrião de Galinha , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Indução Embrionária/genética , Fator 8 de Crescimento de Fibroblasto , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Proteínas com Homeodomínio LIM , Cristalino/embriologia , Fatores de Transcrição Maf , Mesoderma , Fator de Transcrição Associado à Microftalmia , Proteínas do Tecido Nervoso/genética , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados , Epitélio Pigmentado Ocular/embriologia , Proteínas Repressoras , Retina/embriologia , Fatores de Transcrição/metabolismoRESUMO
Depression has been reported in several studies to be more common in Parkinson's disease (PD) patients than in the general population, and there may be overlap in the pathophysiology of the two conditions. Anxiety and other mental disorders have also been examined for possible association with PD because of their effects on the brain. MEDLINE, EMBASE and PSYCHINFO databases were searched systematically for existing systematic reviews or meta-analyses and primary research articles. Past studies and reviews have focused on co-morbidity of depression or mental disorders and PD, but as yet there have been no systematic reviews of the evidence that these conditions precede PD. Articles without robust methodology were excluded by specified criteria, based on published quality scoring criteria. Three cohort studies, one nested case-control study, and 10 case-control studies are included in the current systematic review. Premorbid depression was significantly more common in PD patients than in those without a diagnosis of PD in five of six case-control studies and three cohort studies. Premorbid anxiety may also be associated with PD although the evidence was not as strong. A few studies have looked at dementia as a co-morbid or sequel, but never as a predictor of PD.