SILK studies - capturing the turnover of proteins linked to neurodegenerative diseases.

Autor: Paterson RW; Dementia Research Centre, Department of Neurodegeneration, University College London (UCL) Institute of Neurology, London, UK. r.paterson@ucl.ac.uk., Gabelle A; Department of Neurology, Memory Research and Resources Centre, Centre Hospitalier Universitaire (CHU), Montpellier, France.; University of Montpellier, Campus Universitaire du Triolet, Montpellier, France.; INSERM U1163, Institut de Médecine Régénérative, Saint Eloi Hospital, Montpellier, France., Lucey BP; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Barthélemy NR; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Leckey CA; Department of Neurodegenerative Disease, University College London (UCL) Institute of Neurology, London, UK., Hirtz C; Department of Neurology, Memory Research and Resources Centre, Centre Hospitalier Universitaire (CHU), Montpellier, France.; University of Montpellier, Campus Universitaire du Triolet, Montpellier, France.; INSERM U1163, Institut de Médecine Régénérative, Saint Eloi Hospital, Montpellier, France., Lehmann S; Department of Neurology, Memory Research and Resources Centre, Centre Hospitalier Universitaire (CHU), Montpellier, France.; University of Montpellier, Campus Universitaire du Triolet, Montpellier, France.; INSERM U1163, Institut de Médecine Régénérative, Saint Eloi Hospital, Montpellier, France., Sato C; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Patterson BW; Department of Medicine, Washington University School of Medicine, St Louis, MO, USA., West T; C2N Diagnostics, Center for Emerging Technologies, St Louis, MO, USA., Yarasheski K; C2N Diagnostics, Center for Emerging Technologies, St Louis, MO, USA., Rohrer JD; Dementia Research Centre, Department of Neurodegeneration, University College London (UCL) Institute of Neurology, London, UK., Wildburger NC; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Schott JM; Dementia Research Centre, Department of Neurodegeneration, University College London (UCL) Institute of Neurology, London, UK., Karch CM; Department of Psychiatry, Washington University, St Louis, MO, USA., Wray S; Department of Neurodegenerative Disease, University College London (UCL) Institute of Neurology, London, UK., Miller TM; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Elbert DL; Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, USA., Zetterberg H; Dementia Research Centre, Department of Neurodegeneration, University College London (UCL) Institute of Neurology, London, UK.; UK Dementia Research Institute at University College London (UCL), London, UK.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden., Fox NC; Dementia Research Centre, Department of Neurodegeneration, University College London (UCL) Institute of Neurology, London, UK., Bateman RJ; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
Jazyk: angličtina
Zdroj: Nature reviews. Neurology [Nat Rev Neurol] 2019 Jul; Vol. 15 (7), pp. 419-427. Date of Electronic Publication: 2019 Jun 20.
DOI: 10.1038/s41582-019-0222-0
Abstrakt: Alzheimer disease (AD) is one of several neurodegenerative diseases characterized by dysregulation, misfolding and accumulation of specific proteins in the CNS. The stable isotope labelling kinetics (SILK) technique is based on generating amino acids labelled with naturally occurring stable (that is, nonradioactive) isotopes of carbon and/or nitrogen. These labelled amino acids can then be incorporated into proteins, enabling rates of protein production and clearance to be determined in vivo and in vitro without the use of radioactive or chemical labels. Over the past decade, SILK studies have been used to determine the turnover of key pathogenic proteins amyloid-β (Aβ), tau and superoxide dismutase 1 (SOD1) in the cerebrospinal fluid of healthy individuals, patients with AD and those with other neurodegenerative diseases. These studies led to the identification of several factors that alter the production and/or clearance of these proteins, including age, sleep and disease-causing genetic mutations. SILK studies have also been used to measure Aβ turnover in blood and within brain tissue. SILK studies offer the potential to elucidate the mechanisms underlying various neurodegenerative disease mechanisms, including neuroinflammation and synaptic dysfunction, and to demonstrate target engagement of novel disease-modifying therapies.
Databáze: MEDLINE
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