Inhibition of tumour necrosis factor alpha in the R6/2 mouse model of Huntington’s disease by etanercept treatment

Inhibition of tumour necrosis factor alpha in the R6/2 mouse model of Huntington’s disease by etanercept treatment

Publication date: May 10, 2019

Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by the expansion of the CAG repeat in exon 1 of the huntingtin (HTT) gene, which results in a mutant protein with an extended polyglutamine tract. Inflammation occurs in both the brain and the periphery of HD patients and mouse models, with increases in brain and/or plasma levels of neurotoxic TNFα and several other proinflammatory cytokines. TNFα promotes the generation of many of these cytokines, such as IL6, which raises the possibility that TNFα is central to the inflammatory milieu associated with HD. A number of mouse studies have reported that the suppression of chronic immune activation during HD has beneficial consequences. Here, we investigated whether TNFα contributes to the peripheral inflammation that occurs in the R6/2 mouse model, and whether the in vivo blockade of TNFα, via etanercept treatment, can modify disease progression. We found that etanercept treatment normalised the elevated plasma levels of some cytokines. This did not modify the progression of certain behavioural measures, but slightly ameliorated brain weight loss, possibly related to a reduction in the elevated striatal level of soluble TNFα.

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Pido-Lopez, Jeffrey, Tanudjojo, Benedict, Farag, Sahar, Bondulich, Marie-Katrin, Andre, Ralph, Tabrizi, Sarah J.., and Bates, Gillian P.. Inhibition of tumour necrosis factor alpha in the R6/2 mouse model of Huntington’s disease by etanercept treatment. 06478. 2019 Scientific Reports (9):1.

Concepts Keywords
Blockade Alpha
Brain Inflammation
Cytokines Inflammatory cytokine
Etanercept Interleukin 6
Exon TNF inhibitors
Gene Etanercept
Huntingtin Immunosuppressants
IL6 Cytokines
Inflammation Medicine
Mutant Immunology
Neurodegenerative Disorder Branches of biology
Neurotoxic Medical specialties
Normalised Neurodegenerative disorder
Plasma Inhibition tumour necrosis
Striatal Peripheral inflammation
TNF
Tumour Necrosis Factor
Weight Loss

Semantics

Type Source Name
gene UNIPROT PRDM6
gene UNIPROT KNTC1
gene UNIPROT TNMD
gene UNIPROT CYLD
drug DRUGBANK Tretamine
gene UNIPROT MENT
drug DRUGBANK Trestolone
drug DRUGBANK Albendazole
drug DRUGBANK Tromethamine
drug DRUGBANK Esomeprazole
gene UNIPROT SALL1
gene UNIPROT RRAD
gene UNIPROT RBFOX2
gene UNIPROT MRGPRF
gene UNIPROT BLNK
gene UNIPROT SDS
gene UNIPROT SBDS
drug DRUGBANK Sodium lauryl sulfate
gene UNIPROT ATP5F1B
gene UNIPROT B2M
gene UNIPROT KIT
gene UNIPROT TUB
gene UNIPROT DYRK3
gene UNIPROT IK
drug DRUGBANK Edetic Acid
drug DRUGBANK Water
gene UNIPROT TUBE1
gene UNIPROT TNFSF14
gene UNIPROT DDX53
disease DOID CBA
gene UNIPROT LARGE1
disease MESH autoimmune diseases
gene UNIPROT EDNRA
disease DOID anxiety
disease MESH anxiety
drug DRUGBANK Pentaerythritol tetranitrate
gene UNIPROT GRIP1
gene UNIPROT TSPO
gene UNIPROT CHRM3
gene UNIPROT NOVA2
disease MESH Multiple
disease DOID rheumatoid arthritis
disease MESH rheumatoid arthritis
disease MESH syndromes
gene UNIPROT TCF3
gene UNIPROT TNFRSF1B
gene UNIPROT HCLS1
gene UNIPROT SIGLEC7
gene UNIPROT KHSRP
gene UNIPROT CUX1
gene UNIPROT PSIP1
gene UNIPROT IL2RA
gene UNIPROT PSMD12
gene UNIPROT FOS
gene UNIPROT PIK3R3
gene UNIPROT ERG
gene UNIPROT TNFRSF1A
disease MESH Dementia
disease DOID neurotoxicity
gene UNIPROT MAGEE1
gene UNIPROT SLC6A4
disease MESH trinucleotide repeat expansion
gene UNIPROT SMIM10L2A
gene UNIPROT IL2
gene UNIPROT SMIM10L2B
gene UNIPROT TNF
gene UNIPROT IL6
disease MESH disease progression
disease MESH weight loss
drug DRUGBANK Coenzyme M
pathway BSID Neurodegenerative Diseases
pathway BSID Immune System
gene UNIPROT IL10
gene UNIPROT SLC35G1
gene UNIPROT DEPP1
gene UNIPROT GOPC
gene UNIPROT IL1A
disease MESH cognitive declines
disease MESH psoriasis
disease DOID psoriasis
pathway BSID Rheumatoid arthritis
gene UNIPROT FSCN1
gene UNIPROT TNFSF13
gene UNIPROT ANP32B
disease DOID Dementia
disease MESH Inflammation
gene UNIPROT HTT
disease MESH neurodegenerative disorder
drug DRUGBANK Etanercept

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