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IKKβ signaling medi...
IKKβ signaling mediates metabolic changes in the hypothalamus of a Huntington disease mouse model
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- Soylu-Kucharz, Rana (författare)
- Lund University,Lunds universitet,Biomarkörer vid hjärnsjukdomar,Forskargrupper vid Lunds universitet,Translationell neuroendokrinologi,Biomarkers in Brain Disease,Lund University Research Groups,Translational Neuroendocrinology
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- Khoshnan, Ali (författare)
- California Institute of Technology
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- Petersén, Åsa (författare)
- Lund University,Lunds universitet,Translationell neuroendokrinologi,Forskargrupper vid Lunds universitet,Translational Neuroendocrinology,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- Engelska.
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:2, s. 1-16
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Abstract
Ämnesord
Stäng
- Huntington disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene. Metabolic changes are associated with HD progression, but underlying mechanisms are not fully known. As the IKKβ/NF-κB pathway is an essential regulator of metabolism, we investigated the involvement of IKKβ, the upstream activator of NF-κB in hypothalamus-specific HD metabolic changes. We expressed amyloidogenic N-terminal fragments of mutant HTT (mHTT) in the hypothalamus of mice with brain-specific ablation of IKKβ (Nestin/IKKβlox/lox) and control mice (IKKβlox/lox). We assessed effects on body weight, metabolic hormones, and hypothalamic neuropathology. Hypothalamic expression of mHTT led to an obese phenotype only in female mice. CNS-specific inactivation of IKKβ prohibited weight gain in females, which was independent of neuroprotection and microglial activation. Our study suggests that mHTT in the hypothalamus causes metabolic imbalance in a sex-specific fashion, and central inhibition of the IKKβ pathway attenuates the obese phenotype.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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