Mislocalization of Nucleocytoplasmic Transport Proteins in Human Huntington’s Disease PSC-Derived Striatal Neurons

Lange, Jenny; Wood‐Kaczmar, Alison; Ali, Aneesa; Farag, Sahar; Ghosh, Rhia; Parker, Jennifer; Casey, Caroline; Uno, Yumiko; Kunugi, Akiyoshi; Ferretti, Patrizia; André, Ralph; Tabrizi, Sarah J.

doi:10.3389/fncel.2021.742763

Cited by 17 publications

(9 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Not all cellular dysfunctions mediated by HD mutations extend to glial cells. Indeed, nuclear pore deficits is identified in striatal neurons derived from patient iPSCs but not in astrocytes derived from the same cells [138].…”

Section: Huntington's Diseasementioning

confidence: 99%

Modeling and Targeting Neuroglial Interactions with Human Pluripotent Stem Cell Models

Bigarreau

Rouach

Perrier

et al. 2022

IJMS

View full text Add to dashboard Cite

Generation of relevant and robust models for neurological disorders is of main importance for both target identification and drug discovery. The non-cell autonomous effects of glial cells on neurons have been described in a broad range of neurodegenerative and neurodevelopmental disorders, pointing to neuroglial interactions as novel alternative targets for therapeutics development. Interestingly, the recent breakthrough discovery of human induced pluripotent stem cells (hiPSCs) has opened a new road for studying neurological and neurodevelopmental disorders “in a dish”. Here, we provide an overview of the generation and modeling of both neuronal and glial cells from human iPSCs and a brief synthesis of recent work investigating neuroglial interactions using hiPSCs in a pathophysiological context.

show abstract

Section: Huntington's Diseasementioning

confidence: 99%

Modeling and Targeting Neuroglial Interactions with Human Pluripotent Stem Cell Models

Bigarreau

Rouach

Perrier

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…There is increasing evidence that mutant huntingtin disrupts the nucleocytoplasmic transport and the NPC function. New studies indeed suggest that defects in the NPC might be an important pathogenic mechanism and could possibly become a new therapeutic avenue for HD [46,47,48,49].…”

Section: Resultsmentioning

confidence: 99%

Collaborative network analysis for the interpretation of transcriptomics data in rare diseases, an application to Huntington’s disease

Özışık

Kara

Abbassi-Daloii

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Rare diseases may affect the quality of life of patients and in some cases be life-threatening. Therapeutic opportunities are often limited, in part because of the lack of understanding of the molecular mechanisms that can cause disease. This can be ascribed to the low prevalence of rare diseases and therefore the lower sample sizes available for research. A way to overcome this is to integrate experimental rare disease data with prior knowledge using network-based methods. Taking this one step further, we hypothesized that combining and analyzing the results from multiple network-based methods could provide data-driven hypotheses of pathogenicity mechanisms from multiple perspectives. Results: We analyzed a Huntington's disease (HD) transcriptomics dataset using six network-based methods in a collaborative way. These methods either inherently reported enriched annotation terms or their results were fed into enrichment analyses. The resulting significantly enriched Reactome pathways were then summarized using the ontological hierarchy which allowed the integration and interpretation of outputs from multiple methods. Among the resulting enriched pathways, there are pathways that have been shown previously to be involved in HD and pathways whose direct contribution to disease pathogenesis remains unclear and requires further investigation. Conclusions: In summary, our study shows that collaborative network analysis approaches are well-suited to study rare diseases, as they provide hypotheses for pathogenic mechanisms from multiple perspectives. Applying different methods to the same case study can uncover different disease mechanisms that would not be apparent with the application of a single method.

show abstract

“…This clearance was suggested to be a result of improved the fusion of autophagosomes with lysosomes improving the autophagic flux due to global reduction of O-GlcNAcylation [ 117 , 141 ] suggesting the importance of O-GlcNacylation in regulating autophagy. Further nucleoporin (NUP), important for nucleocytoplasmic transport, was found to be misplaced in the HD mouse model (R6/2, zQ175), fly models, neurons transfected with mHTT, HD iPSC-derived neurons, and human HD brain regions [ 117 , 142 – 144 ]. NUP is also heavily O-GlcNAcylated.…”

Section: O-glcnacylationmentioning

confidence: 99%

Glycosylation and behavioral symptoms in neurological disorders

2023

View full text Add to dashboard Cite

Glycosylation, the addition of glycans or carbohydrates to proteins, lipids, or other glycans, is a complex post-translational modification that plays a crucial role in cellular function. It is estimated that at least half of all mammalian proteins undergo glycosylation, underscoring its importance in the functioning of cells. This is reflected in the fact that a significant portion of the human genome, around 2%, is devoted to encoding enzymes involved in glycosylation. Changes in glycosylation have been linked to various neurological disorders, including Alzheimer’s disease, Parkinson’s disease, autism spectrum disorder, and schizophrenia. Despite its widespread occurrence, the role of glycosylation in the central nervous system remains largely unknown, particularly with regard to its impact on behavioral abnormalities in brain diseases. This review focuses on examining the role of three types of glycosylation: N-glycosylation, O-glycosylation, and O-GlcNAcylation, in the manifestation of behavioral and neurological symptoms in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.

show abstract

Mislocalization of Nucleocytoplasmic Transport Proteins in Human Huntington’s Disease PSC-Derived Striatal Neurons

Cited by 17 publications

References 69 publications

Modeling and Targeting Neuroglial Interactions with Human Pluripotent Stem Cell Models

Modeling and Targeting Neuroglial Interactions with Human Pluripotent Stem Cell Models

Collaborative network analysis for the interpretation of transcriptomics data in rare diseases, an application to Huntington’s disease

Glycosylation and behavioral symptoms in neurological disorders

Contact Info

Product

Resources

About