Oligodendrocytes, the Forgotten Target of Gene Therapy DOI Creative Commons
Yasemin Güneş, Catherine Le Stunff, Pierre Bougnères

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 1973 - 1973

Published: Nov. 28, 2024

If the billions of oligodendrocytes (OLs) populating central nervous system (CNS) patients could express their feelings, they would undoubtedly tell gene therapists about frustration with other neural cell populations, neurons, microglia, or astrocytes, which have been favorite targets transfer experiments. This review questions why OLs left out most therapy attempts. The first explanation is that pathogenic role still discussed in CNS diseases. Another reason so-called ubiquitous CAG, CBA, CBh, CMV promoters—widely used studies—are unable poorly able to activate transcription episomal transgene copies brought by adeno-associated virus (AAV) vectors OLs. Accordingly, expression has either not found evaluated studies rodents non-human primates. aims current are give rightful place among cells future target and encourage researchers test effect OL transduction various

Language: Английский

Autism Spectrum Disorder- and/or Intellectual Disability-Associated Semaphorin-5A Exploits the Mechanism by Which Dock5 Signalosome Molecules Control Cell Shape DOI Creative Commons

Miyu Okabe,

Takanari Sato,

Mikito Takahashi

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(4), P. 3092 - 3107

Published: April 2, 2024

Autism spectrum disorder (ASD) is a neurodevelopmental that includes autism, Asperger’s syndrome, and pervasive developmental disorder. Individuals with ASD may exhibit difficulties in social interactions, communication challenges, repetitive behaviors, restricted interests. While genetic mutations individuals can either activate or inactivate the activities of gene product, impacting neuronal morphogenesis causing symptoms, underlying mechanism remains to be fully established. Herein, for first time, we report genetically conserved Rac1 guanine-nucleotide exchange factor (GEF) Dock5 signalosome molecules control process elongation N1E-115 cell line, model line capable achieving morphological changes. The increased phenotypes observed intellectual disability (ID)-associated Semaphorin-5A (Sema5A) Arg676-to-Cys [p.R676C] were also mediated by molecules. Indeed, knockdown using clustered regularly interspaced short palindromic repeat (CRISPR)/CasRx-based guide(g)RNA specifically recovered mutated Sema5A-induced increase cells. Knockdown Elmo2, an adaptor molecule Dock5, exhibited similar recovery. Comparable results obtained when transfecting interaction region Elmo2. activation c-Jun N-terminal kinase (JNK), one primary signal transduction elongation, was ameliorated their transfection. These suggest comprises abnormal signaling involved induced ASD- ID-associated Sema5A. could added list potential therapeutic target at molecular cellular levels.

Language: Английский

Citations

0
Exposed wires: A microbial metabolite influences myelination in the brain DOI
Brittany D. Needham

Science, Journal Year: 2024, Volume and Issue: 385(6704), P. 37 - 37

Published: July 4, 2024

A microbial metabolite influences myelination in the brain.

Language: Английский

Citations

0
A pontine-specific axonal niche supports de novo gliomagenesis DOI
Zhigang Xie,

Adrija Pathak,

Vytas A. Bankaitis

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 7, 2024

Diffuse intrinsic pontine gliomas (DIPGs), a major type of pediatric high-grade located in the pons, are leading cause death children with brain cancer. A subset (20-25%) DIPGs harbor lysine 27-to-methionine (K27M) mutation

Language: Английский

Citations

0
Cholinergic Neuronal Activity Promotes Diffuse Midline Glioma Growth through Muscarinic Signaling DOI Creative Commons
Richard Drexler, Antonia Drinnenberg, Avishai Gavish

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Neuronal activity promotes the proliferation of healthy oligodendrocyte precursor cells (OPC) and their malignant counterparts, gliomas. Many gliomas arise from closely resemble oligodendroglial lineage precursors, including diffuse midline glioma (DMG), a cancer affecting structures such as thalamus, brainstem spinal cord. In DMG, glutamatergic GABAergic neuronal progression through both paracrine signaling bona-fide neuron-to-glioma synapses. However, putative roles other subpopulations - especially neuromodulatory neurons located in that project to long-range target sites anatomical locations where DMGs remain largely unexplored. Here, we demonstrate cholinergic midbrain modulates OPC DMG circuit-specific manner at projections. Optogenetic stimulation pedunculopontine nucleus (PPN) growth pons, while laterodorsal tegmentum (LDT) facilitates consistent with predominant projection patterns each nucleus. Reciprocal was evident, increased PPN LDT observed pontine DMG-bearing mice. co-culture, hiPSC-derived form networks robustly promote proliferation. Single-cell RNA sequencing analyses revealed prominent expression muscarinic receptor genes

Language: Английский

Citations

0
Oligodendrocytes, the Forgotten Target of Gene Therapy DOI Creative Commons
Yasemin Güneş, Catherine Le Stunff, Pierre Bougnères

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 1973 - 1973

Published: Nov. 28, 2024

If the billions of oligodendrocytes (OLs) populating central nervous system (CNS) patients could express their feelings, they would undoubtedly tell gene therapists about frustration with other neural cell populations, neurons, microglia, or astrocytes, which have been favorite targets transfer experiments. This review questions why OLs left out most therapy attempts. The first explanation is that pathogenic role still discussed in CNS diseases. Another reason so-called ubiquitous CAG, CBA, CBh, CMV promoters—widely used studies—are unable poorly able to activate transcription episomal transgene copies brought by adeno-associated virus (AAV) vectors OLs. Accordingly, expression has either not found evaluated studies rodents non-human primates. aims current are give rightful place among cells future target and encourage researchers test effect OL transduction various

Language: Английский

Citations

0