Tuberous Sclerosis Complex Research

The Activation of the Transcription Factor NRF2 in Epithelial Cells Lining the Kidney Cysts in Tuberous Sclerosis Complex (TSC): The Interplay of Fumarate Hydratase 1, KEAP1, and NRF2 in Kidney Cystogenesis

This paper investigates the role of NRF2 activation in TSC kidney cysts, showing its involvement in metabolic reprogramming and cyst expansion through glutaminolysis.

Metformin modulates autophagy in heterozygous and CRISPR-edited TSC2 primary fibroblasts

This study shows that metformin restores autophagy in TSC2 haploinsufficient and CRISPR-edited fibroblasts by blocking mTORC1, suggesting a potential therapeutic strategy for TSC.

Genome-wide functional genomics screens identify therapeutic vulnerabilities for lymphangioleiomyomatosis

Differentiating TSC2-null human pluripotent stem cells into neural crest cells models lymphangioleiomyomatosis and reveals TWIST1 and SUN4 as synthetic lethal targets whose antisense knockdown eradicates mouse allograft tumors.

An integrated, scaled approach to resolve TSC2 variants of uncertain significance

Abundance scores for 8,891 TSC2 missense variants, plus mTOR pathway activity scores for 391, were calibrated to ACMG/AMP evidence. They putatively reclassify 212 of 276 clinical-cohort missense VUS.

Decoding Lymphangioleiomyomatosis (LAM) Niche Environment via Integrative Analysis of Single Cell Multiomics and Spatial Transcriptomics

This study identifies two distinct LAM subtypes and their microenvironmental interactions using multi-omics and spatial transcriptomics, revealing key regulatory networks and potential therapeutic targets.

The phosphoproteomic landscape of the neurological manifestations in tuberous sclerosis complex

This study performs phosphoproteomic analysis of TSC brain lesions, finding strong mTORC1 activation and widespread mRNA splicing changes in SEGAs but not tubers.

Rac1 contributes to brain connectivity impairments and neuropsychiatric disorders in Tuberous Sclerosis Complex

This study shows Rac1 inhibition reduces anxiety-like behavior and restores brain connectivity in TSC zebrafish mutants by modulating mTORC1 signaling and gene expression.

Extracellular Matrix-Induced Genes May Reduce Response to Rapamycin in LAM

This study identifies extracellular matrix genes that reduce rapamycin response in LAM cells and suggests repurposed inhibitors as potential therapies.

Multiplex imaging combined to machine learning enable automated profiling of cortical malformations applications in tuberous sclerosis complex

This paper uses multiplex imaging and machine learning to profile cortical malformations in tuberous sclerosis complex, identifying key cell types and spatial patterns in lesions.

mTOR dysregulation induces IL6 and paracrine AT2 cell senescence impeding lung repair in lymphangioleiomyomatosis

This study shows mTOR dysregulation in LAM causes IL6 production and senescence in AT2 cells, impairing lung repair, and suggests targeting IL6 may help.

Cerebral Organoids Uncover Mechanisms of Neural Activity Changes in Epileptogenesis

This paper uses cerebral organoids to model Tuberous Sclerosis Complex and identifies mechanisms of neural activity changes in epileptogenesis, showing potential for drug testing.

A Bitopic mTORC Inhibitor Reverses Neural Phenotypes in a Tuberous Sclerosis Complex Murine Model of SEGA-like Hamartomas

This study shows that Rapalink-1, a bitopic mTORC1 inhibitor, reverses neural phenotypes in a TSC SEGA mouse model by reducing hamartoma size and dendrite arbors.

mTORC1 activation drives astrocyte reactivity in cortical tubers and brain organoid models of TSC

This study shows that mTORC1 activation in astrocytes drives reactivity in cortical tubers and brain organoids, linking it to TSC pathology.

TSC1 mRNA processing alterations in tuberous sclerosis complex (TSC) patients with negative or inconclusive genetic testing results

This study identifies mRNA processing errors in TSC patients with negative or inconclusive genetic tests using cDNA analysis, reclassifying a variant of uncertain significance as pathogenic.

Human TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA Methylome

This study shows that TSC2 mutant cells exhibit early neurodevelopmental abnormalities and DNA methylation changes, suggesting early gene regulation disruption in TSC.

STAT1 Promotes PD-L1 Activation and Tumor Growth in Lymphangioleiomyomatosis

This study identifies STAT1 as a driver of LAM cell survival and tumor growth by promoting PD-L1 expression and immune evasion in TSC2-deficient models.

Single-cell profiling of cortical tubers in tuberous sclerosis complex shows molecular structure preservation and massive reorganization of metabolism

The paper uses single-nucleus RNA sequencing to analyze cortical tubers in TSC, finding preserved neuronal subtypes and metabolic reorganization in neurons.

Longitudinal multi-omics reveals pathogenic TSC2 variants disrupt developmental trajectories of human cortical organoids derived from Tuberous Sclerosis Complex

This study uses longitudinal multi-omics analysis of cortical organoids to show that TSC2 pathogenic variants disrupt neurodevelopmental trajectories, leading to synaptic and mitochondrial dysfunction.

Multiparameter Quantitative Analyses of Diagnostic Cells in Brain Tissues from Tuberous Sclerosis Complex

The paper develops a machine learning tool to identify balloon cells in TSC brain tissues using imaging mass cytometry and a custom antibody panel.

TSC2 loss in neural progenitor cells suppresses translation of ASD/NDD-associated transcripts in an mTORC1- and MNK1/2-reversible fashion

This study shows that TSC2 loss in neural progenitor cells suppresses translation of ASD/NDD-associated transcripts, which can be reversed by inhibiting mTORC1 or MNK1/2.

Discovery of novel compounds and target mechanisms using a high throughput, multiparametric phenotypic screen in a human neuronal model of Tuberous Sclerosis

The paper identifies chemical scaffolds that rescue functional TSC disease parameters through a phenotypic screen in a human neuronal model of Tuberous Sclerosis.

Raptor downregulation rescues neuronal phenotypes in mouse models of Tuberous Sclerosis Complex

This study shows that reducing Raptor, a component of mTORC1, improves TSC-related brain phenotypes in mouse models, suggesting it as a potential therapeutic target.

Evaluation of folliculin detection by immunohistochemistry in Birt-Hogg-Dube associated kidney tumors

This study evaluates four commercial anti-FLCN antibodies for immunohistochemistry in BHD-associated kidney tumors but finds none are reliably effective for routine diagnostic use.

Frequency of FLCN Loss of Function Variants and Birt-Hogg-Dube-Associated Phenotypes in a Healthcare System Population

The paper estimates the prevalence of FLCN pathogenic variants and BHD-related phenotypes in a healthcare population, finding a higher frequency than previously reported and underdiagnosis of BHD.

Tsc1 haploinsufficiency leads to Pax2 dysregulation in the developing murine cerebellum

This paper investigates how Tsc1 haploinsufficiency affects cerebellar development in mice, finding dysregulated Pax2 expression and mTOR pathway changes linked to ASD-like phenotypes.

Genetic Insight into Birt-Hogg-Dube syndrome in Indian patients reveals novel mutations in FLCN

The paper identifies novel FLCN mutations in Indian BHDS patients and highlights the role of MTHFR SNPs in disease diagnosis.

Role of type I interferon signaling and microglia in the abnormal long term potentiation and object place recognition deficits of male mice with a mutation of the Tuberous Sclerosis 2 gene

This study shows that microglia and type I interferon signaling contribute to memory and long-term potentiation deficits in male Tsc2+/- mice, which can be reversed by microglia depletion or interferon receptor manipulation.

Tuberin levels during cellular differentiation in brain development

This study examines Tuberin levels during embryonic brain development and finds they decrease in the Purkinje cell layer and during neuronal differentiation.

Folliculin variants linked to Birt-Hogg-Dube syndrome are targeted for proteasomal degradation

The paper shows that BHD-linked FLCN variants cause loss of function via proteasomal degradation and misfolding, with potential therapeutic implications for stabilization.

A human TSC1 mutation screening platform in GABAergic cortical interneurons for Genotype to Phenotype assessments

This study assesses how TSC1 missense variants affect cortical inhibitory interneurons, revealing some variants can partially restore function while others show specific deficits.