Biallelic mutations in SUPV3L1 cause an inherited neurodevelopmental disorder with variable leukodystrophy due to aberrant mitochondrial double stranded RNA processing DOI Creative Commons

Lydia Green,

Noémie Hamilton, Marilena Elpidorou

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Май 10, 2024

Abstract We describe eighteen individuals from twelve families with an autosomal recessive neurodevelopmental disorder and variable leukodystrophy harbouring biallelic variants in SUPV3L1. SUPV3L1 encodes the RNA helicase SUV3 (also known as SUPV3L1), previous studies demonstrating a role for protein part of mitochondrial degradosome. Patient mutations result accumulation double stranded RNAs human cells. An assessment supv3l1 knock-out zebrafish confirmed supv3l1 neurodevelopment, gross defects identified biogenesis microglial function. Zebrafish displayed significant activation type 1 interferon pathway, which was supported by qPCR blood four patients mutations. Altogether, we clinico-radiological spectrum associated mutations, that loss function results altered biogenesis, increased RNA, dysplastic microglia innate immune pathway.

Язык: Английский

Lactylation of Histone H3k18 and Egr1 Promotes Endothelial Glycocalyx Degradation in Sepsis‐Induced Acute Lung Injury DOI Creative Commons
Zongqing Lu, Pu Fang, Shuai Li

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 25, 2024

Abstract Circulating lactate is a critical biomarker for sepsis‐induced acute lung injury (S‐ALI) and strongly associated with poor prognosis. However, whether elevated directly promotes S‐ALI the specific mechanism involved remain unclear. Here, this work shows that causes pulmonary endothelial glycocalyx degradation worsens ALI during sepsis. Mechanistically, increases lactylation of K18 histone H3, which enriched at promoter EGR1 its transcription, leading to upregulation heparanase in microvascular cells. In addition, multiple sites are identified EGR1, confirmed occur mainly K364. K364 facilitates interaction importin‐α, turn promoting nuclear localization. Importantly, identifies KAT2B as novel lactyltransferase whose GNAT domain mediates S‐ALI. vivo, suppression production or genetic knockout mitigated improved survival outcomes mice polymicrobial Therefore, study reveals crosstalk between metabolic reprogramming cells epigenetic modifications plays role pathological processes

Язык: Английский

Процитировано

1
Inflammation macrophages contribute to cardiac homeostasis DOI Creative Commons
Yu Zhang,

Junchu Tu,

Yujie Li

и другие.

Cardiology Plus, Год журнала: 2023, Номер 8(1), С. 6 - 17

Опубликована: Янв. 1, 2023

Cardiovascular diseases (CVDs) have high morbidity. Many endogenous and exogenous factors provoke the innate immune response causing tissue damage accelerating progression of diseases. The macrophages are major cells mediating inflammatory response. Inflammasomes multi-protein complexes that recognize danger signals, activate cytokines, participate in Both inflammasomes play a critical role development CVDs, such as myocardial infarction, hypertension, atherosclerosis. This review will summarize studies on discuss potential therapeutic interventions. Moreover, distinct inflammation process, but closely linked. inflammasome system occur macrophages, macrophage pyroptosis may be provoked by activation. cytokines secreted related to activation inflammasomes, further heart cause interconversion M1 phenotype M2 phenotype. mechanism regulating polarization remains investigated.

Язык: Английский

Процитировано

3
PNPT1 Spectrum Disorders: An Underrecognized and Complex Group of Neurometabolic Disorders DOI Creative Commons
Paulo Victor Sgobbi de Souza, Igor Braga Farias, Paulo de Lima Serrano

и другие.

Muscles, Год журнала: 2024, Номер 3(1), С. 4 - 15

Опубликована: Янв. 19, 2024

An 18-year-old man presented with slowly progressive infancy-onset spasticity of the lower limbs and cerebellar ataxia, associated painless strabismus, intellectual disability, urinary incontinence, bilateral visual loss, cognitive decline since early adolescence. A neurological examination disclosed spastic dysarthria, left eye divergent ophthalmoparesis, impaired smooth pursuit, severe paraparesis global brisk tendon reflexes, extensor plantar responses, ankle clonus reflex. Bilateral dysdiadochokinesia upper limbs, Stewart-Holmes rebound phenomenon, dysmetria, a abnormal finger-to-nose test were observed. Markedly reduced acuity (right side 20/150, 20/400) moderate to optic atrophy detected. Neuroimaging studies showed nerves tract as main findings. As complicated Hereditary Spastic Paraplegia, autosomal dominant Spinocerebellar Ataxia, or inherited neurometabolic disorders suspected, large next-generation sequencing-based gene panel testing heterozygous pathogenic variant c.162-1G>A in intron 1 PNPT1 gene. diagnosis PNPT1-related ataxia was established. Clinicians must be aware possibility variants cases paraplegias that are marked decline, regardless established family history compromise.

Язык: Английский

Процитировано

0
Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia DOI Creative Commons
Yulin Huang, Rui Xu, Qi Liu

и другие.

BMC Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Май 7, 2024

Sleep loss is a common public health problem that causes hyperalgesia, especially after surgery, which reduces the quality of life seriously.

Язык: Английский

Процитировано

0
Biallelic mutations in SUPV3L1 cause an inherited neurodevelopmental disorder with variable leukodystrophy due to aberrant mitochondrial double stranded RNA processing DOI Creative Commons

Lydia Green,

Noémie Hamilton, Marilena Elpidorou

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Май 10, 2024

Abstract We describe eighteen individuals from twelve families with an autosomal recessive neurodevelopmental disorder and variable leukodystrophy harbouring biallelic variants in SUPV3L1. SUPV3L1 encodes the RNA helicase SUV3 (also known as SUPV3L1), previous studies demonstrating a role for protein part of mitochondrial degradosome. Patient mutations result accumulation double stranded RNAs human cells. An assessment supv3l1 knock-out zebrafish confirmed supv3l1 neurodevelopment, gross defects identified biogenesis microglial function. Zebrafish displayed significant activation type 1 interferon pathway, which was supported by qPCR blood four patients mutations. Altogether, we clinico-radiological spectrum associated mutations, that loss function results altered biogenesis, increased RNA, dysplastic microglia innate immune pathway.

Язык: Английский

Процитировано

0