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Sökning: WFRF:(Nedergaard L) > (2020)

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1.
  • Isidor, Marie S., et al. (författare)
  • Pyruvate kinase M2 represses thermogenic gene expression in brown adipocytes
  • 2020
  • Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 594:7, s. 1218-1225
  • Tidskriftsartikel (refereegranskat)abstract
    • Utilizing the thermogenic capacity of brown adipose tissue is a potential anti-obesity strategy; therefore, the mechanisms controlling expression of thermogenesis-related genes are of interest. Pyruvate kinase (PK) catalyzes the last step of glycolysis and exists as four isoenzymes: PK, liver, PK, red blood cell, PK, muscle (PKM1 and PKM2). PKM2 has both glycolytic and nuclear functions. Here, we report that PKM2 is enriched in brown adipose compared with white adipose tissue. Specific knockdown of PKM2 in mature brown adipocytes demonstrates that silencing of PKM2 does not lead to a decrease in PK activity, but causes a robust upregulation of thermogenic uncoupling protein 1 (Ucp1) and fibroblast growth factor 21 (Fgf21) gene expression. This increase is not mediated by any of the known mechanisms for PKM2-regulated gene expression, thus implying the existence of a novel mechanism for PKM2-dependent effects on gene expression.
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2.
  • Reeves, Benjamin C., et al. (författare)
  • Glymphatic System Impairment in Alzheimer's Disease and Idiopathic Normal Pressure Hydrocephalus
  • 2020
  • Ingår i: Trends in Molecular Medicine. - : Elsevier BV. - 1471-4914. ; 26:3, s. 285-295
  • Forskningsöversikt (refereegranskat)abstract
    • Approximately 10% of dementia patients have idiopathic normal pressure hydrocephalus (iNPH), an expansion of the cerebrospinal fluid (CSF)-filled brain ventricles. iNPH and Alzheimer's disease (AD) both exhibit sleep disturbances, build-up of brain metabolic wastes and amyloid-β (Aβ) plaques, perivascular reactive astrogliosis, and mislocalization of astrocyte aquaporin-4 (AQP4). The glia–lymphatic (glymphatic) system facilitates brain fluid clearance and waste removal during sleep via glia-supported perivascular channels. Human studies have implicated impaired glymphatic function in both AD and iNPH. Continued investigation into the role of glymphatic system biology in AD and iNPH models could lead to new strategies to improve brain health by restoring homeostatic brain metabolism and CSF dynamics.
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