alpha-Synuclein: a Modulator During Inflammatory CNS Demyelination.

Publication date: Mar 23, 2020

Neuroinflammation and demyelination are hallmarks of several neurological disorders such as multiple sclerosis and multiple system atrophy. To better understand the underlying mechanisms of de- and regeneration in respective diseases, it is critical to identify factors modulating these processes. One candidate factor is alpha-Synuclein (aSyn), which is known to be involved in the pathology of various neurodegenerative diseases. Recently, we have shown that aSyn is involved in the modulation of peripheral immune responses during acute neuroinflammatory processes. In the present study, the effect of aSyn deficiency on de- and regenerative events in the CNS was analyzed by using two different demyelinating animal models: chronic MOG-induced experimental autoimmune encephalomyelitis (EAE) and the cuprizone model. Histopathological analysis of spinal cord cross sections 8 weeks after EAE induction revealed a significant reduction of CNS inflammation accompanied by decreased myelin loss during late-stage inflammatory demyelination in aSyn-deficient mice. In contrast, after cuprizone-induced demyelination or remyelination following withdrawal of cuprizone, myelination and neuroinflammatory patterns were not affected by aSyn deficiency. These data provide further evidence for aSyn as regulator of peripheral immune responses under neuroinflammatory conditions, thereby also modulating degenerative events in late-stage demyelinating disease.

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Kuhbandner, K., Hoffmann, A., Gonz’alez Alvarado, M.N., Seyler, L., B”auerle, T., Winkler, J., and Linker, R.A. alpha-Synuclein: a Modulator During Inflammatory CNS Demyelination. 20526. 2020 J Mol Neurosci.

Concepts Keywords
Cross Alpha
Demyelinating Disease Neuroinflammation
Demyelination Remyelination
Histopathological Demyelinating disease
Inflammation Experimental autoimmune encephalomyelitis
Mice Neurological disorders
Modulation Animal testing
MOG Neurology
Multiple Sclerosis Multiple sclerosis
Multiple System Atrophy Medical specialties
Myelin Nervous system
Myelination Organ systems
Neurodegenerative Diseases Multiple sclerosis
Neurological Disorders ASyn deficiency
Pathology Multiple system atrophy
Spinal Cord Demyelination
Regeneration respective diseases


Type Source Name
pathway KEGG Colorectal cancer
disease MESH colorectal cancer
disease MESH sclerosis
disease MESH myelitis
disease MESH glioma
pathway KEGG Glioma
drug DRUGBANK Trestolone
disease MESH brain inflammation
disease MESH autoimmunity
disease MESH men
disease MESH cognitive decline
drug DRUGBANK Tromethamine
drug DRUGBANK Doxycycline
drug DRUGBANK Acetate ion
drug DRUGBANK Nitrogen
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK Potassium Chloride
drug DRUGBANK Alpha-methyltryptamine
disease MESH diagnosis
drug DRUGBANK Isoxaflutole
drug DRUGBANK Phosphate ion
drug DRUGBANK Ethanol
drug DRUGBANK Microcrystalline cellulose
drug DRUGBANK Formaldehyde
drug DRUGBANK Isoflurane
disease MESH separation
drug DRUGBANK Ornithine
drug DRUGBANK Streptomycin
drug DRUGBANK Benzylpenicillin
drug DRUGBANK Basic Fibroblast Growth Factor
pathway KEGG Glycerophospholipid metabolism
drug DRUGBANK Flavin adenine dinucleotide
drug DRUGBANK Indoleacetic acid
disease MESH growth
disease MESH syndrome
disease MESH defects
drug DRUGBANK Bexarotene
drug DRUGBANK KD3010
pathway KEGG Sphingolipid metabolism
pathway KEGG Fatty acid degradation
pathway KEGG Fatty acid biosynthesis
pathway KEGG PPAR signaling pathway
drug DRUGBANK Levocarnitine
drug DRUGBANK Coenzyme A
drug DRUGBANK Stearic acid
drug DRUGBANK Activated charcoal
drug DRUGBANK Omega-3 fatty acids
drug DRUGBANK Coenzyme M
disease MESH dissociation
pathway KEGG Fatty acid elongation
pathway KEGG Fatty acid metabolism
drug DRUGBANK Phosphatidylethanolamine
disease MESH weight loss
disease MESH paralysis
disease MESH paresis
disease MESH gait ataxia
disease MESH tremors
drug DRUGBANK Pyridoxal Phosphate
disease MESH gliosis
drug DRUGBANK Proline
disease MESH ***P
drug DRUGBANK Tamoxifen
pathway KEGG Metabolic pathways
drug DRUGBANK Methionine
drug DRUGBANK Hexadecanal
pathway KEGG Peroxisome
pathway KEGG Melanoma
disease MESH Melanoma
disease MESH Carcinogenesis
disease MESH primary progressive multiple sclerosis
drug DRUGBANK Oleic Acid
drug DRUGBANK Cholesterol
disease MESH aging
disease MESH death
disease MESH CNS diseases
disease MESH inflammation
disease MESH pathology
disease MESH neurodegenerative diseases
pathway REACTOME Neurodegenerative Diseases
disease MESH experimental autoimmune encephalomyelitis
drug DRUGBANK Tropicamide
disease MESH multiple system atrophy
disease MESH multiple sclerosis
disease MESH neurological disorders
disease MESH demyelination


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