Oligodendrocyte-Specific Mechanisms of Myelin Thinning: Implications for Neurodegenerative Diseases

Sen, Monokesh Kumer; Hossain, Jakir

doi:10.3389/fnins.2021.663053

Cited by 3 publications

(2 citation statements)

References 32 publications

(60 reference statements)

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“…Demyelination leads to the disruption of action potential propagation and the generation of myelin fragments as debris. New myelin formation at the site of CNS demyelination occurs through the maturation of oligodendrocyte progenitor cells (OPCs) followed by remyelination (reviewed in Nave & Werner, 2014; Sen & Hossain, 2021; Sen et al, 2019b; Snaidero & Simons, 2014). Remyelination is necessary to restore myelin structure, provide metabolic support to axons, and restore rapid action potential propagation along axons.…”

Section: Introductionmentioning

confidence: 99%

The roles of microglia and astrocytes in phagocytosis and myelination: Insights from the cuprizone model of multiple sclerosis

Sen

Mahns

Coorssen

et al. 2022

Glia

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In human demyelinating diseases such as multiple sclerosis (MS), an imbalance between demyelination and remyelination can trigger progressive degenerative processes. The clearance of myelin debris (phagocytosis) from the site of demyelination by microglia is critically important to achieve adequate remyelination and to slow the progression of the disease. However, how microglia phagocytose the myelin debris, and why clearance is impaired in MS, is not fully known; likewise, the role of the microglia in remyelination remains unclear. Recent studies using cuprizone (CPZ) as an animal model of central nervous system demyelination revealed that the up‐regulation of signaling proteins in microglia facilitates effective phagocytosis of myelin debris. Moreover, during demyelination, protective mediators are released from activated microglia, resulting in the acceleration of remyelination in the CPZ model. In contrast, inadequate microglial activation or recruitment to the site of demyelination, and the production of toxic mediators, impairs remyelination resulting in progressive demyelination. In addition to the microglia‐mediated phagocytosis, astrocytes play an important role in the phagocytic process by recruiting microglia to the site of demyelination and producing regenerative mediators. The current review is an update of these emerging findings from the CPZ animal model, discussing the roles of microglia and astrocytes in phagocytosis and myelination.

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Section: Introductionmentioning

confidence: 99%

The roles of microglia and astrocytes in phagocytosis and myelination: Insights from the cuprizone model of multiple sclerosis

Sen

Mahns

Coorssen

et al. 2022

Glia

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“…This suggests that proteins were misfolded and eventually aggregated [ 208 , 276 ]. Such protein interactions can enhance oligodendrocyte degeneration that subsequently results in demyelination [ 277 , 278 , 279 ]. For example, endoplasmic reticulum-induced stress response (measured by overexpression of the folding enzyme disulphide isomerase) leads to apoptosis of oligodendrocytes [ 280 ].…”

Section: Differentially Abundant Canonical Proteins In Ms and Animal Modelsmentioning

confidence: 99%

Proteomics of Multiple Sclerosis: Inherent Issues in Defining the Pathoetiology and Identifying (Early) Biomarkers

Sen

Almuslehi

Shortland

et al. 2021

IJMS

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Multiple Sclerosis (MS) is a demyelinating disease of the human central nervous system having an unconfirmed pathoetiology. Although animal models are used to mimic the pathology and clinical symptoms, no single model successfully replicates the full complexity of MS from its initial clinical identification through disease progression. Most importantly, a lack of preclinical biomarkers is hampering the earliest possible diagnosis and treatment. Notably, the development of rationally targeted therapeutics enabling pre-emptive treatment to halt the disease is also delayed without such biomarkers. Using literature mining and bioinformatic analyses, this review assessed the available proteomic studies of MS patients and animal models to discern (1) whether the models effectively mimic MS; and (2) whether reasonable biomarker candidates have been identified. The implication and necessity of assessing proteoforms and the critical importance of this to identifying rational biomarkers are discussed. Moreover, the challenges of using different proteomic analytical approaches and biological samples are also addressed.

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Advanced theragnostics for the central nervous system (CNS) and neurological disorders using functional inorganic nanomaterials

Conklin

Conley

Hou

et al. 2023

Advanced Drug Delivery Reviews

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Oligodendrocyte-Specific Mechanisms of Myelin Thinning: Implications for Neurodegenerative Diseases

Cited by 3 publications

References 32 publications

The roles of microglia and astrocytes in phagocytosis and myelination: Insights from the cuprizone model of multiple sclerosis

The roles of microglia and astrocytes in phagocytosis and myelination: Insights from the cuprizone model of multiple sclerosis

Proteomics of Multiple Sclerosis: Inherent Issues in Defining the Pathoetiology and Identifying (Early) Biomarkers

Advanced theragnostics for the central nervous system (CNS) and neurological disorders using functional inorganic nanomaterials

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