Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Int J Mol Sci ; 22(21)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34768952

RESUMO

The fact that Parkinson's disease (PD) pathologies are well advanced in most PD patients by the time of clinical elucidation attests to the importance of early diagnosis. Our attempt to achieve this has capitalized on our previous finding that GM1 ganglioside is expressed at subnormal levels in virtually all tissues of sporadic PD (sPD) patients including blood cells. GM1 is present in most vertebrate cells, is especially abundant in neurons where it was shown essential for their effective functioning and long term viability. We have utilized peripheral blood mononuclear cells (PBMCs) which, despite their low GM1, we found to be significantly lower in sPD patients compared to age-matched healthy controls. To quantify GM1 (and GD1a) we used high performance thin-layer chromatography combined with cholera toxin B linked to horseradish peroxidase, followed by densitometric quantification. GM1 was also deficient in PBMCs from PD patients with mutations in the glucocerebrosidase gene (PD-GBA), apparently even lower than in sPD. Reasons are given why we believe these results obtained with patients manifesting fully developed PD will apply as well to PD patients in preclinical stages-a topic for future study. We also suggest that these findings point to a potential disease altering therapy for PD once the early diagnosis is established.


Assuntos
Gangliosídeo G(M1)/sangue , Gangliosídeo G(M1)/deficiência , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , Idoso , Biomarcadores/sangue , Análise Química do Sangue , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Gangliosídeos/sangue , Glucosilceramidase/genética , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Doença de Parkinson/genética , Curva ROC
2.
Exp Neurol ; 329: 113284, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32165255

RESUMO

Parkinson's disease (PD) is a major neurodegenerative disorder characterized by a variety of non-motor symptoms in addition to the well-recognized motor dysfunctions that have commanded primary interest. We previously described a new PD mouse model based on heterozygous disruption of the B4galnt1 gene leading to partial deficiency of the GM1 family of gangliosides that manifested several nigrostriatal neuropathological features of PD as well as movement impairment. We now show this mouse also suffers three non-motor symptoms characteristic of PD involving the gastrointestinal, sympathetic cardiac, and cerebral cognitive systems. Treatment of these animals with a synthetic form of GM1 ganglioside, produced by transfected E. coli, proved ameliorative of these symptoms as well as the motor defect. These findings further suggest subnormal GM1 to be a systemic defect constituting a major risk factor in sporadic PD and indicate the B4galnt1(+/-) (HT) mouse to be a true neuropathological model that recapitulates both motor and non-motor lesions of this condition.


Assuntos
Modelos Animais de Doenças , Gangliosídeo G(M1)/administração & dosagem , Gangliosídeo G(M1)/deficiência , N-Acetilgalactosaminiltransferases/deficiência , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Animais , Feminino , Gangliosídeo G(M1)/genética , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/genética , Gastroenteropatias/metabolismo , Masculino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/genética , Transtornos da Memória/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Transtornos das Habilidades Motoras/tratamento farmacológico , Transtornos das Habilidades Motoras/genética , Transtornos das Habilidades Motoras/metabolismo , N-Acetilgalactosaminiltransferases/genética , Doença de Parkinson/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...