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Article ; Online: A retroviral link to vertebrate myelination through retrotransposon-RNA-mediated control of myelin gene expression.

Ghosh, Tanay / Almeida, Rafael G / Zhao, Chao / Mannioui, Abdelkrim / Martin, Elodie / Fleet, Alex / Chen, Civia Z / Assinck, Peggy / Ellams, Sophie / Gonzalez, Ginez A / Graham, Stephen C / Rowitch, David H / Stott, Katherine / Adams, Ian / Zalc, Bernard / Goldman, Nick / Lyons, David A / Franklin, Robin J M

Cell

2024 Volume 187, Issue 4, Page(s) 814–830.e23

Abstract: Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in the central nervous system (CNS). This evolutionary innovation, which first appears in jawed vertebrates, enabled rapid transmission of nerve impulses, more ... ...

Abstract	Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in the central nervous system (CNS). This evolutionary innovation, which first appears in jawed vertebrates, enabled rapid transmission of nerve impulses, more complex brains, and greater morphological diversity. Here, we report that RNA-level expression of RNLTR12-int, a retrotransposon of retroviral origin, is essential for myelination. We show that RNLTR12-int-encoded RNA binds to the transcription factor SOX10 to regulate transcription of myelin basic protein (Mbp, the major constituent of myelin) in rodents. RNLTR12-int-like sequences (which we name RetroMyelin) are found in all jawed vertebrates, and we further demonstrate their function in regulating myelination in two different vertebrate classes (zebrafish and frogs). Our study therefore suggests that retroviral endogenization played a prominent role in the emergence of vertebrate myelin.
MeSH term(s)	Animals ; Gene Expression ; Myelin Sheath/metabolism ; Oligodendroglia/metabolism ; Retroelements/genetics ; RNA/metabolism ; Zebrafish/genetics ; Anura
Chemical Substances	Retroelements ; RNA (63231-63-0)
Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2024.01.011
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Article ; Online: microRNA dysregulation in polyglutamine toxicity of TATA-box binding protein is mediated through STAT1 in mouse neuronal cells.

Roshan, Reema / Choudhary, Ashwani / Bhambri, Aksheev / Bakshi, Bhawani / Ghosh, Tanay / Pillai, Beena

Journal of neuroinflammation

2017 Volume 14, Issue 1, Page(s) 155

Abstract: Background: Polyglutamine diseases constitute a class of neurodegenerative disorders associated with expansion of the cytosine-adenine-guanine (CAG) triplet, in protein coding genes. Expansion of a polyglutamine tract in the N-terminal of TBP is the ... ...

Abstract	Background: Polyglutamine diseases constitute a class of neurodegenerative disorders associated with expansion of the cytosine-adenine-guanine (CAG) triplet, in protein coding genes. Expansion of a polyglutamine tract in the N-terminal of TBP is the causal mutation in SCA17. Brain sections of patients with spinocerebellar ataxia 17 (SCA17), a type of neurodegenerative disease, have been reported to contain protein aggregates of TATA-binding protein (TBP). It is also implicated in other neurodegenerative diseases like Huntington's disease, since the protein aggregates formed in such diseases also contain TBP. Dysregulation of miR-29a/b is another common feature of neurodegenerative diseases including Alzheimer's disease, Huntington's disease, and SCA17. Using a cellular model of SCA17, we identified key connections in the molecular pathway from protein aggregation to miRNA dysregulation. Methods: Gene expression profiling was performed subsequent to the expression of TBP containing polyglutamine in a cellular model of SCA17. We studied the expression of STAT1 and other interferon-gamma dependent genes in neuronal apoptosis. The molecular pathway leading to the dysregulation of miRNA in response of protein aggregation and interferon release was investigated using RNAi-mediated knockdown of STAT1. Results: We show that the accumulation of polyglutamine-TBP in the cells results in interferon-gamma release which in turn signals through STAT1 leading to downregulation of miR-29a/b. We propose that the release of interferons by cells harboring toxic protein aggregates may trigger a bystander effect resulting in loss of neurons. Interferon-gamma also led to upregulation of miR-322 although this effect is not mediated through STAT1. Conclusions: Our investigation shows that neuroinflammation could be an important player in mediating the transcriptional dysregulation of miRNA and the subsequent apoptotic effect of toxic polyglutamine-TBP. The involvement of immunomodulators in polyglutamine diseases holds special therapeutic relevance in the light of recent findings that interferon-gamma can modulate behavior.
MeSH term(s)	Animals ; Cell Line, Tumor ; Gene Expression Regulation/genetics ; Gene Expression Regulation/physiology ; Interferon-gamma/genetics ; Interferon-gamma/metabolism ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neuroblastoma/pathology ; Neurons/drug effects ; Neurons/metabolism ; Peptides/genetics ; Peptides/toxicity ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; STAT1 Transcription Factor/genetics ; STAT1 Transcription Factor/metabolism ; TATA-Box Binding Protein/genetics ; TATA-Box Binding Protein/metabolism ; Time Factors ; Transfection
Chemical Substances	IFNG protein, mouse ; MicroRNAs ; Nerve Tissue Proteins ; Peptides ; RNA, Small Interfering ; STAT1 Transcription Factor ; Stat1 protein, mouse ; TATA-Box Binding Protein ; polyglutamine (26700-71-0) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2017--03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1742-2094
ISSN (online)	1742-2094
DOI	10.1186/s12974-017-0925-3
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Article ; Online: Myc determines the functional age state of oligodendrocyte progenitor cells.

Neumann, Björn / Segel, Michael / Ghosh, Tanay / Zhao, Chao / Tourlomousis, Panagiotis / Young, Adam / Förster, Sarah / Sharma, Amar / Chen, Civia Zi-Yu / Cubillos, Juan F / Rawji, Khalil S / Chalut, Kevin J / Franklin, Robin J M

Nature aging

2021 Volume 1, Issue 9, Page(s) 826–837

Abstract: Like many adult stem cell populations, the capacity of oligodendrocyte progenitor cells (OPCs) to proliferate and differentiate is substantially impaired with aging. Previous work has shown that tissue-wide transient expression of the pluripotency ... ...

Abstract	Like many adult stem cell populations, the capacity of oligodendrocyte progenitor cells (OPCs) to proliferate and differentiate is substantially impaired with aging. Previous work has shown that tissue-wide transient expression of the pluripotency factors Oct4, Sox2, Klf4 and c-Myc extends lifespan and enhances somatic cell function. Here we show that just one of these factors, c-Myc, is sufficient to determine the age state of OPC: c-Myc expression in aged OPCs drives their functional rejuvenation, while its inhibition in neonatal OPCs induces an aged-like phenotype, as determined by in vitro assays and transcriptome analysis. Increasing c-Myc expression in aged OPCs in vivo restores their proliferation and differentiation capacity, thereby enhancing regeneration in an aged central nervous system environment. Our results directly link Myc to cellular activity and cell age state, with implications for understanding regeneration in the context of aging, and provide important insights into the biology of stem cell aging.
MeSH term(s)	Oligodendrocyte Precursor Cells/physiology ; Central Nervous System ; Stem Cells/metabolism ; Cell Differentiation/genetics ; Adult Stem Cells
Language	English
Publishing date	2021-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2662-8465
ISSN (online)	2662-8465
DOI	10.1038/s43587-021-00109-4
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Article ; Online: Regulation of BACE1 by miR-29a/b in a cellular model of Spinocerebellar Ataxia 17.

Roshan, Reema / Ghosh, Tanay / Gadgil, Mugdha / Pillai, Beena

RNA biology

2012 Volume 9, Issue 6, Page(s) 891–899

Abstract: Polyglutamine diseases are a class of neurodegenerative disorders characterized by expansion of polyglutamine repeats, protein aggregation and neuronal cell death in specific regions of the brain. The expansion of a polyglutamine repeat in the TATA ... ...

Abstract	Polyglutamine diseases are a class of neurodegenerative disorders characterized by expansion of polyglutamine repeats, protein aggregation and neuronal cell death in specific regions of the brain. The expansion of a polyglutamine repeat in the TATA binding protein (TBP) causes a neurodegenerative disease, Spinocerebellar Ataxia 17 (SCA17). This disease is characterized by intranuclear protein aggregates and selective loss of cerebellar neurons, including Purkinje cells. MicroRNAs are small, endogenous, regulatory non-coding RNA molecules that bind to messenger RNAs with partial complementarity and interfere in their expression. Here, we used a cellular model of SCA17 where we expressed TBP with 16 (normal) or 59 (pathogenic) polyglutamines and found differential expression of several microRNAs. Specifically, we found two microRNAs, miR-29a/b, were down-regulated. With miR-29a/b down regulation, we found an increased expression of targets of miR-29a/b -beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), p53 upregulated modulator of apoptosis (PUMA) and BAK, increased cytochrome c release and apoptosis. Restoration of miR-29a/b in the pathogenic polyglutamine background reduced the BACE1expression. While, antagomiRs against miR-29a/b resulted in an increase in BACE1 levels and neuronal apoptosis. In spite of the elevation of BACE1 in Alzhemiers disease, its role in neuronal cell death has not been established. Here, we show that increased BACE1 expression is not sufficient to cause apoptosis. However restoring level of BACE1 to normal in polyglutamine cells partially reduced neuronal apoptosis. We show a role for the miR-29a/b-BACE1 regulatory interaction in SCA17, suggesting that this microRNA could be part of a common molecular mechanism leading to neuronal cell death in multiple neurodegenerative disorders. The identification of a common mechanism of microRNA mediated neurodegeneration not only improves our understanding of the process, but also provides promising and novel therapeutic targets.
MeSH term(s)	5' Untranslated Regions ; Amyloid Precursor Protein Secretases/genetics ; Amyloid Precursor Protein Secretases/metabolism ; Animals ; Apoptosis ; Aspartic Acid Endopeptidases/genetics ; Aspartic Acid Endopeptidases/metabolism ; Base Sequence ; Binding Sites ; Cell Line ; Cytochromes c/metabolism ; Gene Knockdown Techniques ; Humans ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; MicroRNAs/physiology ; RNA Interference ; RNA, Small Interfering/genetics ; Spinocerebellar Ataxias/genetics ; Spinocerebellar Ataxias/metabolism ; TATA-Box Binding Protein/biosynthesis ; TATA-Box Binding Protein/genetics
Chemical Substances	5' Untranslated Regions ; MIRN29 microRNA, mouse ; MicroRNAs ; RNA, Small Interfering ; TATA-Box Binding Protein ; Cytochromes c (9007-43-6) ; Amyloid Precursor Protein Secretases (EC 3.4.-) ; Aspartic Acid Endopeptidases (EC 3.4.23.-) ; Bace1 protein, mouse (EC 3.4.23.46)
Language	English
Publishing date	2012-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1555-8584
ISSN (online)	1555-8584
DOI	10.4161/rna.19876
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Article ; Online: Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing.

de la Fuente, Alerie G / Queiroz, Rayner M L / Ghosh, Tanay / McMurran, Christopher E / Cubillos, Juan F / Bergles, Dwight E / Fitzgerald, Denise C / Jones, Clare A / Lilley, Kathryn S / Glover, Colin P / Franklin, Robin J M

Molecular & cellular proteomics : MCP

2020 Volume 19, Issue 8, Page(s) 1281–1302

Abstract: Following central nervous system (CNS) demyelination, adult oligodendrocyte progenitor cells (OPCs) can differentiate into new myelin-forming oligodendrocytes in a regenerative process called remyelination. Although remyelination is very efficient in ... ...

Abstract	Following central nervous system (CNS) demyelination, adult oligodendrocyte progenitor cells (OPCs) can differentiate into new myelin-forming oligodendrocytes in a regenerative process called remyelination. Although remyelination is very efficient in young adults, its efficiency declines progressively with ageing. Here we performed proteomic analysis of OPCs freshly isolated from the brains of neonate, young and aged female rats. Approximately 50% of the proteins are expressed at different levels in OPCs from neonates compared with their adult counterparts. The amount of myelin-associated proteins, and proteins associated with oxidative phosphorylation, inflammatory responses and actin cytoskeletal organization increased with age, whereas cholesterol-biosynthesis, transcription factors and cell cycle proteins decreased. Our experiments provide the first ageing OPC proteome, revealing the distinct features of OPCs at different ages. These studies provide new insights into why remyelination efficiency declines with ageing and potential roles for aged OPCs in other neurodegenerative diseases.
MeSH term(s)	Aging/metabolism ; Animals ; Animals, Newborn ; Biomarkers/metabolism ; Cell Separation ; Cholesterol/metabolism ; Myelin Sheath/metabolism ; Neurodegenerative Diseases/pathology ; Oligodendrocyte Precursor Cells/cytology ; Oligodendrocyte Precursor Cells/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Folding ; Proteome/metabolism ; Proteomics ; Proteostasis ; Rats, Sprague-Dawley ; Reproducibility of Results
Chemical Substances	Biomarkers ; Proteome ; Cholesterol (97C5T2UQ7J) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2075924-1
ISSN	1535-9484 ; 1535-9476
ISSN (online)	1535-9484
ISSN	1535-9476
DOI	10.1074/mcp.RA120.002102
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Zs.A 5599: Show issues

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Article ; Online: TBR2 coordinates neurogenesis expansion and precise microcircuit organization via Protocadherin 19 in the mammalian cortex.

Lv, Xiaohui / Ren, Si-Qiang / Zhang, Xin-Jun / Shen, Zhongfu / Ghosh, Tanay / Xianyu, Anjin / Gao, Peng / Li, Zhizhong / Lin, Susan / Yu, Yang / Zhang, Qiangqiang / Groszer, Matthias / Shi, Song-Hai

Nature communications

2019 Volume 10, Issue 1, Page(s) 3946

Abstract: Cerebral cortex expansion is a hallmark of mammalian brain evolution; yet, how increased neurogenesis is coordinated with structural and functional development remains largely unclear. The T-box protein TBR2/EOMES is preferentially enriched in ... ...

Abstract	Cerebral cortex expansion is a hallmark of mammalian brain evolution; yet, how increased neurogenesis is coordinated with structural and functional development remains largely unclear. The T-box protein TBR2/EOMES is preferentially enriched in intermediate progenitors and supports cortical neurogenesis expansion. Here we show that TBR2 regulates fine-scale spatial and circuit organization of excitatory neurons in addition to enhancing neurogenesis in the mouse cortex. TBR2 removal leads to a significant reduction in neuronal, but not glial, output of individual radial glial progenitors as revealed by mosaic analysis with double markers. Moreover, in the absence of TBR2, clonally related excitatory neurons become more laterally dispersed and their preferential synapse development is impaired. Interestingly, TBR2 directly regulates the expression of Protocadherin 19 (PCDH19), and simultaneous PCDH19 expression rescues neurogenesis and neuronal organization defects caused by TBR2 removal. Together, these results suggest that TBR2 coordinates neurogenesis expansion and precise microcircuit assembly via PCDH19 in the mammalian cortex.
MeSH term(s)	Animals ; Cadherins/genetics ; Cadherins/metabolism ; Cerebral Cortex/cytology ; Cerebral Cortex/embryology ; Cerebral Cortex/metabolism ; Gene Expression Profiling/methods ; Gene Expression Regulation, Developmental ; HEK293 Cells ; Humans ; Mice, Knockout ; Mice, Transgenic ; Neurogenesis/genetics ; Neurons/metabolism ; RNA Interference ; Synapses/metabolism ; T-Box Domain Proteins/genetics ; T-Box Domain Proteins/metabolism
Chemical Substances	Cadherins ; Eomes protein, mouse ; Pcdh19 protein, mouse ; T-Box Domain Proteins
Language	English
Publishing date	2019-09-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-019-11854-x
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Article ; Online: MicroRNAs: novel therapeutic targets in neurodegenerative diseases.

Roshan, Reema / Ghosh, Tanay / Scaria, Vinod / Pillai, Beena

Drug discovery today

2009 Volume 14, Issue 23-24, Page(s) 1123–1129

Abstract: The prevalence of neurodegenerative disorders is rising steadily as human life expectancy increases. However, limited knowledge of the molecular basis of disease pathogenesis is a major hurdle in the identification of drug targets and development of ... ...

Abstract	The prevalence of neurodegenerative disorders is rising steadily as human life expectancy increases. However, limited knowledge of the molecular basis of disease pathogenesis is a major hurdle in the identification of drug targets and development of therapeutic strategies for these largely incurable disorders. Recently, differential expression of endogenous regulatory small RNAs, known as 'microRNAs' (miRNAs), in patients of Alzheimer's disease, Parkinson's disease and models of ataxia suggest that they might have key regulatory roles in neurodegeneration. miRNAs that can target known mediators of neurodegeneration offer potential therapeutic targets. Our bioinformatic analysis suggests novel miRNA-target interactions that could potentially influence neurodegeneration. The recent development of molecules that alter miRNA expression promises valuable tools that will enhance the therapeutic potential of miRNAs.
MeSH term(s)	Animals ; Brain/metabolism ; Genetic Predisposition to Disease ; Humans ; MicroRNAs/physiology ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/therapy
Chemical Substances	MicroRNAs
Language	English
Publishing date	2009-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1324988-5
ISSN	1878-5832 ; 1359-6446
ISSN (online)	1878-5832
ISSN	1359-6446
DOI	10.1016/j.drudis.2009.09.009
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Zs.A 4725: Show issues

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Article ; Online: Altered social behavior in mice carrying a cortical Foxp2 deletion.

Medvedeva, Vera P / Rieger, Michael A / Vieth, Beate / Mombereau, Cédric / Ziegenhain, Christoph / Ghosh, Tanay / Cressant, Arnaud / Enard, Wolfgang / Granon, Sylvie / Dougherty, Joseph D / Groszer, Matthias

Human molecular genetics

2018 Volume 28, Issue 5, Page(s) 701–717

Abstract: Genetic disruptions of the forkhead box transcription factor FOXP2 in humans cause an autosomal-dominant speech and language disorder. While FOXP2 expression pattern are highly conserved, its role in specific brain areas for mammalian social behaviors ... ...

Abstract	Genetic disruptions of the forkhead box transcription factor FOXP2 in humans cause an autosomal-dominant speech and language disorder. While FOXP2 expression pattern are highly conserved, its role in specific brain areas for mammalian social behaviors remains largely unknown. Here we studied mice carrying a homozygous cortical Foxp2 deletion. The postnatal development and gross morphological architecture of mutant mice was indistinguishable from wildtype (WT) littermates. Unbiased behavioral profiling of adult mice revealed abnormalities in approach behavior towards conspecifics as well as in the reciprocal responses of WT interaction partners. Furthermore mutant mice showed alterations in acoustical parameters of ultrasonic vocalizations, which also differed in function of the social context. Cell type-specific gene expression profiling of cortical pyramidal neurons revealed aberrant regulation of genes involved in social behavior. In particular Foxp2 mutants showed the downregulation of Mint2 (Apba2), a gene involved in approach behavior in mice and autism spectrum disorder in humans. Taken together these data demonstrate that cortical Foxp2 is required for normal social behaviors in mice.
MeSH term(s)	Animals ; Behavior, Animal ; Cerebral Cortex/diagnostic imaging ; Cerebral Cortex/metabolism ; Cerebral Cortex/pathology ; Cerebral Cortex/physiopathology ; Forkhead Transcription Factors/deficiency ; Gene Deletion ; Homozygote ; Mice ; Mice, Knockout ; Neurons/metabolism ; Repressor Proteins/deficiency ; Social Behavior
Chemical Substances	Forkhead Transcription Factors ; Foxp2 protein, mouse ; Repressor Proteins
Language	English
Publishing date	2018-09-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddy372
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Zs.A 3469: Show issues

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Article ; Online: Correction to: Niacin-mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system.

Acta neuropathologica

2020 Volume 139, Issue 5, Page(s) 911

Abstract: The article Niacin‑mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system, written by Khalil S. Rawji, Adam M.H. Young, Tanay Ghosh, Nathan J. Michaels, Reza Mirzaei, Janson Kappen, Kathleen L. ... ...

Abstract	The article Niacin‑mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system, written by Khalil S. Rawji, Adam M.H. Young, Tanay Ghosh, Nathan J. Michaels, Reza Mirzaei, Janson Kappen, Kathleen L. Kolehmainen, Nima Alaeiilkhchi, Brian Lozinski, Manoj K. Mishra, Annie Pu, Weiwen Tang, Salma Zein, Deepak K. Kaushik, Michael B. Keough, Jason R. Plemel, Fiona Calvert, Andrew J. Knights, Daniel J. Gaffney, Wolfram Tetzlaff, Robin J. M. Franklin and V. Wee Yong, was originally published electronically on the publisher's internet.
Language	English
Publishing date	2020-03-24
Publishing country	Germany
Document type	Journal Article ; Published Erratum
ZDB-ID	1079-0
ISSN	1432-0533 ; 0001-6322
ISSN (online)	1432-0533
ISSN	0001-6322
DOI	10.1007/s00401-020-02146-6
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Article ; Online: Niacin-mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system.

Acta neuropathologica

2020 Volume 139, Issue 5, Page(s) 893–909

Abstract: Remyelination following CNS demyelination restores rapid signal propagation and protects axons; however, its efficiency declines with increasing age. Both intrinsic changes in the oligodendrocyte progenitor cell population and extrinsic factors in the ... ...

Abstract	Remyelination following CNS demyelination restores rapid signal propagation and protects axons; however, its efficiency declines with increasing age. Both intrinsic changes in the oligodendrocyte progenitor cell population and extrinsic factors in the lesion microenvironment of older subjects contribute to this decline. Microglia and monocyte-derived macrophages are critical for successful remyelination, releasing growth factors and clearing inhibitory myelin debris. Several studies have implicated delayed recruitment of macrophages/microglia into lesions as a key contributor to the decline in remyelination observed in older subjects. Here we show that the decreased expression of the scavenger receptor CD36 of aging mouse microglia and human microglia in culture underlies their reduced phagocytic activity. Overexpression of CD36 in cultured microglia rescues the deficit in phagocytosis of myelin debris. By screening for clinically approved agents that stimulate macrophages/microglia, we have found that niacin (vitamin B3) upregulates CD36 expression and enhances myelin phagocytosis by microglia in culture. This increase in myelin phagocytosis is mediated through the niacin receptor (hydroxycarboxylic acid receptor 2). Genetic fate mapping and multiphoton live imaging show that systemic treatment of 9-12-month-old demyelinated mice with therapeutically relevant doses of niacin promotes myelin debris clearance in lesions by both peripherally derived macrophages and microglia. This is accompanied by enhancement of oligodendrocyte progenitor cell numbers and by improved remyelination in the treated mice. Niacin represents a safe and translationally amenable regenerative therapy for chronic demyelinating diseases such as multiple sclerosis.
MeSH term(s)	Aging/physiology ; Animals ; Axons/pathology ; Demyelinating Diseases/pathology ; Humans ; Macrophages/pathology ; Mice, Transgenic ; Microglia/metabolism ; Microglia/pathology ; Multiple Sclerosis/pathology ; Niacin/metabolism ; Phagocytosis/physiology ; Rejuvenation/physiology ; Remyelination/physiology
Chemical Substances	Niacin (2679MF687A)
Language	English
Publishing date	2020-02-06
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1079-0
ISSN	1432-0533 ; 0001-6322
ISSN (online)	1432-0533
ISSN	0001-6322
DOI	10.1007/s00401-020-02129-7
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