Role of glucose 6-phosphate dehydrogenase (G6PD) deficiency and its association to Autism Spectrum Disorders

Mondal, Abir; Mukherjee, Soumyadeep; Dar, Waseem; Singh, Shailja; Pati, Soumya

doi:10.1016/j.bbadis.2021.166185

Cited by 5 publications

(4 citation statements)

References 75 publications

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“…Baixos níveis de NADPH já foram associados com o autismo, o que sugere que a deficiência da G6PD pode contribuir para o desbalanço do estresse oxidativo na patogênese do TEA 15 . Além disso, a deficiência de G6PD ativaria microglias e astrócitos por uma cascata de sinalização que envolve citocinas e aumento de espécies reativas de oxigênio, que podem gerar neuroinflamação, que, em última instância, causa disfunção sináptica, hipomielinização e morte de neurônios 8 . A neuroinflamação já foi relacionada como uma das principais contribuintes de muitas doenças neurodegenerativas e condições neuropsiquiátricas 3 .…”

Section: Discussionunclassified

“…Nesse sentido, já foram observados em tecido cerebral post-mortem de 11 indivíduos autistas processos neuroinflamatórios ativos no córtex cerebral, na substância branca e no cerebelo 17 . Entretanto, o mecanismo completo da neuroinflamação na TEA ainda não foi totalmente elucidado 8 .…”

Section: Discussionunclassified

“…A G6PD também atua no metabolismo do ácido fólico, que usa na biossíntese a NADPH, sendo que sua deficiência gera diminuição do metabolismo desta vitamina, prejudicando o desenvolvimento do sistema nervoso e a formação de sinapses, o que gera diminuição das funções cognitivas, contribuindo para o surgimento de doenças neurológicas 8 . Ademais, a deficiência dele resulta no aumento do estresse oxidativo do eritrócito, diminuindo sua sobrevida e provocando hemólise e anemia hemolítica.…”

Section: Discussionunclassified

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Deficiência Da Glicose-6-Fosfato Desidrogenase Em Paciente Com Transtorno Do Espectro Autista

DUARTE

Pegoraro

Maglioni

et al. 2022

RMP

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Section: Discussionunclassified

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Deficiência Da Glicose-6-Fosfato Desidrogenase Em Paciente Com Transtorno Do Espectro Autista

DUARTE

Pegoraro

Maglioni

et al. 2022

RMP

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“…It is very evident that the degree of G6PD deficiency also represents diverse pathophysiology. Recently, diabetes, cardiovascular disorders, and neurological disorders were reported to be associated with G6PD deficiency [8][9][10][11][12][13]. So, G6PD-deficient patients are highly susceptible to develop diverse pathophysiology and may also show severe outcomes during infections.…”

Section: Introductionmentioning

confidence: 99%

G6PD deficiency mediated impairment of iNOS and lysosomal acidification affecting phagocytotic clearance in microglia in response to SARS-CoV-2

Mondal,

Munan,

Saxena

et al. 2023

Preprint

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The glucose-6-phosphate dehydrogenase (G6PD) deficiency is X-linked and is the most common enzymatic deficiency disorder globally. It is a crucial enzyme for the pentose phosphate pathway and produces NADPH, which plays a vital role in the regulation of oxidative stress of many cell types. The deficiency of G6PD causes hemolytic anemia, diabetes, cardiovascular and neurological disorders. Notably, the patient with G6PD deficiency was severely affected by SARS-CoV-2 and showed prolonged COVID-19 symptoms, neurological impacts, and high mortality. However, the mechanism of COVID-19 severity in G6PD deficient patients is still ambiguous. Here, using a CRISPR-edited G6PD deficient human microglia cell culture model, we observed a significant reduction in NADPH and an increase in basal reactive oxygen species (ROS) in microglia. Interestingly, the deficiency of the G6PD-NAPDH axis impairs induced nitric oxide synthase (iNOS) mediated nitric oxide (NO) production which plays a fundamental role in inhibiting viral replication. Surprisingly, we also observed that the deficiency of the G6PD-NADPH axis reduced lysosomal acidification, which further abrogates the lysosomal clearance of viral particles. Thus, impairment of NO production and lysosomal acidification as well as redox dysregulation in G6PD deficient microglia altered innate immune response, promoting the severity of SARS-CoV-2 pathogenesis.

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G6PD deficiency mediated impairment of iNOS and lysosomal acidification affecting phagocytotic clearance in microglia in response to SARS-CoV-2

Mondal,

Munan,

Saxena

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Role of glucose 6-phosphate dehydrogenase (G6PD) deficiency and its association to Autism Spectrum Disorders

Cited by 5 publications

References 75 publications

Deficiência Da Glicose-6-Fosfato Desidrogenase Em Paciente Com Transtorno Do Espectro Autista

Deficiência Da Glicose-6-Fosfato Desidrogenase Em Paciente Com Transtorno Do Espectro Autista

G6PD deficiency mediated impairment of iNOS and lysosomal acidification affecting phagocytotic clearance in microglia in response to SARS-CoV-2

G6PD deficiency mediated impairment of iNOS and lysosomal acidification affecting phagocytotic clearance in microglia in response to SARS-CoV-2

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