MCL-1 regulates cellular transitions during oligodendrocyte development DOI Creative Commons
Melanie Gil,

Marina R. Hanna,

Vivian Gama

et al.

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

Published: Dec. 21, 2024

Abstract Oligodendrocytes are the myelinating cells of central nervous system. Regulation early stages oligodendrocyte development is critical to function cell. Specifically, myelin sheath formation an energetically demanding event that requires precision, as alterations may lead dysmyelination. Recent work has established fatty acid β-oxidation required for oligodendrocytes. We have shown MCL-1, a well-characterized anti-apoptotic protein, oligodendrocytes in vivo . Further, it was recently uncovered MCL-1 regulates long- chain through its interaction with acyl-CoA synthetase long-chain family member 1 (ACSL1), enzyme responsible conversion acids into acyl-CoA. Here, we introduce vitro system isolate human stem cell- derived progenitor and investigate involvement during development. Using this system, pharmacologically inhibited (OPCs) elucidate non-apoptotic protein at developmental stage. Additionally, used motor neuron co-culture downstream effects inhibition later when begin contact axons generate basic protein. demonstrate mitochondrial network changes resemble those reported Our findings point factor essential OPC stage proper morphogenesis.

Language: Английский

Altered glia-neuron communication in Alzheimer’s Disease affects WNT, p53, and NFkB Signaling determined by snRNA-seq DOI Creative Commons
Tabea M. Soelter, Timothy C. Howton, Amanda D. Clark

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 7, 2024

Alzheimer's disease is the most common cause of dementia and characterized by amyloid-β plaques, tau neurofibrillary tangles, neuronal loss. Although loss a primary hallmark disease, it known that non-neuronal cell populations are ultimately responsible for maintaining brain homeostasis health through neuron-glia glial crosstalk. Many signaling pathways have been proposed to be dysregulated in including WNT, TGFβ, p53, mTOR, NFkB, Pi3k/Akt signaling. Here, we predict altered cell-cell communication between glia neurons.

Language: Английский

Citations

7
A New Acquaintance of Oligodendrocyte Precursor Cells in the Central Nervous System DOI

Zexuan Ma,

Wei Zhang, C. Wang

et al.

Neuroscience Bulletin, Journal Year: 2024, Volume and Issue: 40(10), P. 1573 - 1589

Published: July 23, 2024

Language: Английский

Citations

7
Glial cell deficits are a key feature of schizophrenia: implications for neuronal circuit maintenance and histological differentiation from classical neurodegeneration DOI Creative Commons
Hans‐Gert Bernstein,

Markus Nußbaumer,

Veronika Vasilevska

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

Abstract Dysfunctional glial cells play a pre-eminent role in schizophrenia pathophysiology. Post-mortem studies have provided evidence for significantly decreased cell numbers different brain regions of individuals with schizophrenia. Reduced are most pronounced oligodendroglia, but reduced astrocyte densities also been reported. This review highlights that oligo- and astroglial deficits key histopathological feature schizophrenia, distinct from typical changes seen neurodegenerative disorders. Significant oligodendrocytes may arise two ways: (i) demise mature functionally compromised oligodendrocytes; (ii) lack due to failed maturation progenitor cells. We analyse detail the controversy regarding astrocytes. Regardless their origin, several pathophysiological consequences. Among these, myelination number be important factor, resulting disconnectivity between neurons observed When die, it appears through degeneration, process which is basically reversible. Thus, therapeutic interventions help rescue or improve might viable option. Since antipsychotic treatment alone does not seem prevent loss deficits, there intense search new options. Current proposals range application antidepressants other chemical agents as well physical exercise engrafting healthy into brains patients.

Language: Английский

Citations

7
Oligodendrocyte precursor cells facilitate neuronal lysosome release DOI Creative Commons
Li‐Pao Fang, Ching-Hsin Lin, Yasser Medlej

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 30, 2025

Abstract Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a activity-dependent manner. These facilitate exocytosis of lysosomes. A reduction the number or branching reduces these contacts, which is associated lysosome accumulation and altered metabolism neurons more senescent age. similar OPC seen an early-stage mouse model Alzheimer’s disease. Our findings have implications for prevention age-related pathologies treatment neurodegenerative diseases.

Language: Английский

Citations

1
The Genomic Intersection of Oligodendrocyte Dynamics in Schizophrenia and Aging Unravels Novel Pathological Mechanisms and Therapeutic Potentials DOI Open Access
Andrea Rivera,

John R. Normanton,

Arthur M. Butt

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4452 - 4452

Published: April 18, 2024

Schizophrenia is a significant worldwide health concern, affecting over 20 million individuals and contributing to potential reduction in life expectancy by up 14.5 years. Despite its profound impact, the precise pathological mechanisms underlying schizophrenia continue remain enigmatic, with previous research yielding diverse occasionally conflicting findings. Nonetheless, one consistently observed phenomenon brain imaging studies of patients disruption white matter, bundles myelinated axons that provide connectivity rapid signalling between regions. Myelin produced specialised glial cells known as oligodendrocytes, which have been shown be disrupted post-mortem analyses patients. Oligodendrocytes are generated throughout major population oligodendrocyte progenitor (OPC), essential for matter plasticity. Notably, decline specific subpopulation OPC has identified principal factor loss aging brain, suggesting this may also schizophrenia. In review, we analysed genomic databases pinpoint intersections identify shared cognitive dysfunction.

Language: Английский

Citations

5
Unlocking the Potential: immune functions of oligodendrocyte precursor cells DOI Creative Commons

Amr Haroon,

Harsha Seerapu,

Li‐Pao Fang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 9, 2024

Oligodendrocyte precursor cells (OPCs) have long been regarded as progenitors of oligodendrocytes, yet recent advances illuminated their multifaceted nature including emerging immune functions. This review seeks to shed light on the functions exhibited by OPCs, spanning from phagocytosis modulation and direct engagement with across various pathological scenarios. Comprehensive understanding OPCs alongside other roles will pave way for targeted therapies in neurological disorders.

Language: Английский

Citations

3
CCL5 is essential for axonogenesis and neuronal restoration after brain injury DOI Creative Commons
Man-Hau Ho, Yih‐Jeng Tsai, Chia-Yen Chen

et al.

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: Sept. 17, 2024

Traumatic brain injury (TBI) causes axon tearing and synapse degradation, resulting in multiple neurological dysfunctions exacerbation of early neurodegeneration; the repair axonal synaptic structures is critical for restoring neuronal function. C-C Motif Chemokine Ligand 5 (CCL5) shows many neuroprotective activities.

Language: Английский

Citations

3
Are oligodendrocytes bystanders or drivers of Parkinson’s disease pathology? DOI Creative Commons
Jorge Campos, Lena F. Burbulla, Sarah Jäkel

et al.

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(1), P. e3002977 - e3002977

Published: Jan. 8, 2025

The major pathological feature of Parkinson ‘s disease (PD), the second most common neurodegenerative and movement disorder, is predominant degeneration dopaminergic neurons in substantia nigra, a part midbrain. Despite decades research, molecular mechanisms origin remain unknown. While was initially viewed as purely neuronal results from single-cell transcriptomics have suggested that oligodendrocytes may play an important role early stages Parkinson’s. Although these findings are high relevance, particularly to search for effective disease-modifying therapies, actual functional Parkinson’s remains highly speculative requires concerted scientific effort be better understood. This Unsolved Mystery discusses limited understanding PD, highlighting unresolved questions regarding changes oligodendroglia, myelin nigral neurons, impact toxic environment, aggregation alpha-synuclein within oligodendrocytes.

Language: Английский

Citations

0
The Role of Glial Cells in the Pathophysiology of Epilepsy DOI Creative Commons
Filiz Onat, My Andersson, Nihan Çarçak

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 94 - 94

Published: Jan. 10, 2025

Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly impacting individuals worldwide. Current treatments are often ineffective for third of patients and can cause severe side effects, necessitating new therapeutic approaches. Glial cells, particularly astrocytes, microglia, oligodendrocytes, emerging as crucial targets in epilepsy management. Astrocytes regulate neuronal homeostasis, excitability, synaptic plasticity, playing key roles maintaining the blood-brain barrier (BBB) mediating neuroinflammatory responses. Dysregulated astrocyte functions, such reactive astrogliosis, lead to abnormal activity seizure generation. They release gliotransmitters, cytokines, chemokines that may exacerbate or mitigate seizures. Microglia, innate immune cells CNS, contribute neuroinflammation, glutamate excitotoxicity, balance between excitatory inhibitory neurotransmission, underscoring their dual role promotion protection. Meanwhile, primarily involved myelination, also modulate axonal excitability neuron-glia network underlying pathogenesis. Understanding dynamic interactions glial with neurons provides promising avenues novel therapies. Targeting these improved control better clinical outcomes, offering hope refractory epilepsy.

Language: Английский

Citations

0
Evaluation of altered cell–cell communication between glia and neurons in the hippocampus of 3xTg‐AD mice at two time points DOI Creative Commons
Tabea M. Soelter, Timothy C. Howton, Elizabeth Wilk

et al.

Journal of Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 19(1)

Published: Feb. 28, 2025

Language: Английский

Citations

0