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View article: The protective PLCγ2-P522R variant mitigates Alzheimer’s disease-associated pathologies by enhancing beneficial microglial functions
The protective PLCγ2-P522R variant mitigates Alzheimer’s disease-associated pathologies by enhancing beneficial microglial functions Open
View article: Three‐dimensional view of microglia—amyloid plaque interactions
Three‐dimensional view of microglia—amyloid plaque interactions Open
Recent gene expression studies have revealed about 10 different states of microglia, some of which are characteristic for Alzheimer‐like amyloid plaque pathology. However, it is not presently known how these translate into morphological fe…
View article: <i>C9orf72</i>repeat expansion-carrying iPSC-microglia from FTD patients show increased phagocytic activity concomitantly with decreased number of autophagosomal-lysosomal vesicles
<i>C9orf72</i>repeat expansion-carrying iPSC-microglia from FTD patients show increased phagocytic activity concomitantly with decreased number of autophagosomal-lysosomal vesicles Open
C9orf72 hexanucleotide repeat expansion (HRE) is a major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. The role of microglia in these C9orf72 HRE-associated diseases is understudied. To elucidate effects of C9…
View article: Treatment of Status Epilepticus after Traumatic Brain Injury Using an Antiseizure Drug Combined with a Tissue Recovery Enhancer Revealed by Systems Biology
Treatment of Status Epilepticus after Traumatic Brain Injury Using an Antiseizure Drug Combined with a Tissue Recovery Enhancer Revealed by Systems Biology Open
We tested a hypothesis that in silico-discovered compounds targeting traumatic brain injury (TBI)-induced transcriptomics dysregulations will mitigate TBI-induced molecular pathology and augment the effect of co-administered antiseizure tr…
View article: Protective Alzheimer's disease-associated APP A673T variant predominantly decreases sAPPβ levels in cerebrospinal fluid and 2D/3D cell culture models
Protective Alzheimer's disease-associated APP A673T variant predominantly decreases sAPPβ levels in cerebrospinal fluid and 2D/3D cell culture models Open
The rare A673T variant was the first variant found within the amyloid precursor protein (APP) gene conferring protection against Alzheimer's disease (AD). Thereafter, different studies have discovered that the carriers of the APP A673T var…
View article: Gene Expression Profile as a Predictor of Seizure Liability
Gene Expression Profile as a Predictor of Seizure Liability Open
Analysis platforms to predict drug-induced seizure liability at an early phase of drug development would improve safety and reduce attrition and the high cost of drug development. We hypothesized that a drug-induced in vitro transcriptomic…
View article: Protective Alzheimer’s disease-associated APP A673T variant predominantly decreases sAPPβ levels in cerebrospinal fluid and 2D/3D cell culture models
Protective Alzheimer’s disease-associated APP A673T variant predominantly decreases sAPPβ levels in cerebrospinal fluid and 2D/3D cell culture models Open
Background:The rare A673T variant was the first variant found within the amyloid precursor protein (APP) gene conferring protection against Alzheimer’s disease (AD). Thereafter, different studies have discovered that the carriers of the AP…
View article: Enhanced drug delivery by a prodrug approach effectively relieves neuroinflammation in mice
Enhanced drug delivery by a prodrug approach effectively relieves neuroinflammation in mice Open
The efficacy of NSAIDs can be improved via the utilization of LAT1 and repurposed for the treatment of neuroinflammation. This improved brain delivery and microglia localisation can be applied to other inflammatory modulators to achieve ef…
View article: C9orf72 hexanucleotide repeat expansion leads to altered neuronal and dendritic spine morphology and synaptic dysfunction
C9orf72 hexanucleotide repeat expansion leads to altered neuronal and dendritic spine morphology and synaptic dysfunction Open
Frontotemporal lobar degeneration (FTLD) comprises a heterogenous group of progressive neurodegenerative syndromes. To date, no validated biomarkers or effective disease-modifying therapies exist for the different clinical or genetic subty…
View article: Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury
Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury Open
We assessed the effect of antioxidant therapy using the Food and Drug Administration-approved respiratory drug N-acetylcysteine (NAC) or sulforaphane (SFN) as monotherapies or duotherapy in vitro in neuron-BV2 microglial co-cultures and va…
View article: MECP2 Increases the Pro-Inflammatory Response of Microglial Cells and Phosphorylation at Serine 423 Regulates Neuronal Gene Expression upon Neuroinflammation
MECP2 Increases the Pro-Inflammatory Response of Microglial Cells and Phosphorylation at Serine 423 Regulates Neuronal Gene Expression upon Neuroinflammation Open
Methyl-CpG-binding protein 2 (MECP2) is a critical transcriptional regulator for synaptic function. Dysfunction of synapses, as well as microglia-mediated neuroinflammation, represent the earliest pathological events in Alzheimer’s disease…
View article: Isoflurane affects brain functional connectivity in rats 1 month after exposure
Isoflurane affects brain functional connectivity in rats 1 month after exposure Open
View article: Presynaptic Vesicle Protein SEPTIN5 Regulates the Degradation of APP C-Terminal Fragments and the Levels of Aβ
Presynaptic Vesicle Protein SEPTIN5 Regulates the Degradation of APP C-Terminal Fragments and the Levels of Aβ Open
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by aberrant amyloid-β (Aβ) and hyperphosphorylated tau aggregation. We have previously investigated the involvement of SEPTIN family members in AD-related cellular proce…
View article: Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques
Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques Open
Background Alzheimer’s disease (AD) is the most common neurodegenerative disease and type 2 diabetes (T2D) plays an important role in conferring the risk for AD. Although AD and T2D share common features, the common molecular mechanisms un…
View article: Genetic and functional studies of genes involved in the pathogenesis of Alzheimer's disease
Genetic and functional studies of genes involved in the pathogenesis of Alzheimer's disease Open
View article: BV-2 Microglial Cells Overexpressing C9orf72 Hexanucleotide Repeat Expansion Produce DPR Proteins and Show Normal Functionality but No RNA Foci
BV-2 Microglial Cells Overexpressing C9orf72 Hexanucleotide Repeat Expansion Produce DPR Proteins and Show Normal Functionality but No RNA Foci Open
Hexanucleotide repeat expansion (HRE) in the chromosome 9 open-reading frame 72 (C9orf72) gene is the most common genetic cause underpinning frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). It…
View article: Diabetic phenotype in mouse and humans with β-amyloid pathology reduces the number of microglia around β-amyloid plaques
Diabetic phenotype in mouse and humans with β-amyloid pathology reduces the number of microglia around β-amyloid plaques Open
Type 2 diabetes (T2D) increases the risk of Alzheimer’s disease (AD). Even though these two diseases share common molecular pathways, the mechanisms remain elusive. To shed light into these mechanisms, mice with different AD- and/or tauopa…
View article: Additional file 9 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques
Additional file 9 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques Open
Additional file 9: Supplementary Table S8. Enrichment analysis for differentially expressed genes upon TWD.
View article: Additional file 7 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques
Additional file 7 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques Open
Additional file 7: Supplementary Table S6. Enrichment analysis for WGCNA module genes.
View article: Additional file 3 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques
Additional file 3 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques Open
Additional file 3: Supplementary Table S2. Differential expression analysis results for AwT+, A+Tw, and A+T+ vs AwTw, TWD mice.
View article: Additional file 8 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques
Additional file 8 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques Open
Additional file 8: Supplementary Table S7. Differential expression analysis results for TWD vs STD mice.
View article: Additional file 4 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques
Additional file 4 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques Open
Additional file 4: Supplementary Table S3. Enrichment analysis for differentially expressed genes in AwT+, A+Tw, and A+T+ vs AwTw comparison for both STD and TWD mice.
View article: Additional file 5 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques
Additional file 5 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques Open
Additional file 5: Supplementary Table S4. Enrichment analysis for genes showing discordant response to β-amyloid- and/or Tau-pathology upon TWD (Fig. 2a, blue dot genes).
View article: Additional file 2 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques
Additional file 2 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques Open
Additional file 2: Supplementary Table S1. Differential expression analysis results for AwT+, A+Tw, and A+T+ vs AwTw, STD mice.
View article: Additional file 6 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques
Additional file 6 of Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques Open
Additional file 6: Supplementary Table S5. WGCNA module assignment and membership values.
View article: In Vitro and In Vivo Pipeline for Validation of Disease-Modifying Effects of Systems Biology-Derived Network Treatments for Traumatic Brain Injury—Lessons Learned
In Vitro and In Vivo Pipeline for Validation of Disease-Modifying Effects of Systems Biology-Derived Network Treatments for Traumatic Brain Injury—Lessons Learned Open
We developed a pipeline for the discovery of transcriptomics-derived disease-modifying therapies and used it to validate treatments in vitro and in vivo that could be repurposed for TBI treatment. Desmethylclomipramine, ionomycin, sirolimu…
View article: C9orf72 Proteins Regulate Autophagy and Undergo Autophagosomal or Proteasomal Degradation in a Cell Type-Dependent Manner
C9orf72 Proteins Regulate Autophagy and Undergo Autophagosomal or Proteasomal Degradation in a Cell Type-Dependent Manner Open
Dysfunctional autophagy or ubiquitin-proteasome system (UPS) are suggested to underlie abnormal protein aggregation in neurodegenerative diseases. Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS)-associated C9orf72 is …
View article: l-Type Amino Acid Transporter 1 (LAT1/Lat1)-Utilizing Prodrugs Can Improve the Delivery of Drugs into Neurons, Astrocytes and Microglia
l-Type Amino Acid Transporter 1 (LAT1/Lat1)-Utilizing Prodrugs Can Improve the Delivery of Drugs into Neurons, Astrocytes and Microglia Open
View article: Altered Insulin Signaling in Alzheimer’s Disease Brain – Special Emphasis on PI3K-Akt Pathway
Altered Insulin Signaling in Alzheimer’s Disease Brain – Special Emphasis on PI3K-Akt Pathway Open
Alzheimer's disease (AD) and type 2 diabetes (T2D) are both diseases with increasing prevalence in aging populations. T2D, characterized by insulin resistance and defective insulin signaling, is a common co-morbidity and a risk factor for …
View article: Astrocytes and Microglia as Potential Contributors to the Pathogenesis of C9orf72 Repeat Expansion-Associated FTLD and ALS
Astrocytes and Microglia as Potential Contributors to the Pathogenesis of C9orf72 Repeat Expansion-Associated FTLD and ALS Open
Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative diseases with a complex, but often overlapping, genetic and pathobiological background and thus they are considered to form a disease sp…