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Nat Rev Neurol. 2019 Jul;15(7):419-427. doi: 10.1038/s41582-019-0222-0. Epub 2019 Jun 20.

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

Author information

1
Dementia Research Centre, Department of Neurodegeneration, University College London (UCL) Institute of Neurology, London, UK. r.paterson@ucl.ac.uk.
2
Department of Neurology, Memory Research and Resources Centre, Centre Hospitalier Universitaire (CHU), Montpellier, France.
3
University of Montpellier, Campus Universitaire du Triolet, Montpellier, France.
4
INSERM U1163, Institut de Médecine Régénérative, Saint Eloi Hospital, Montpellier, France.
5
Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
6
Department of Neurodegenerative Disease, University College London (UCL) Institute of Neurology, London, UK.
7
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
8
C2N Diagnostics, Center for Emerging Technologies, St Louis, MO, USA.
9
Dementia Research Centre, Department of Neurodegeneration, University College London (UCL) Institute of Neurology, London, UK.
10
Department of Psychiatry, Washington University, St Louis, MO, USA.
11
Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, USA.
12
UK Dementia Research Institute at University College London (UCL), London, UK.
13
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
14
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.

Abstract

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.

PMID:
31222062
PMCID:
PMC6876864
DOI:
10.1038/s41582-019-0222-0
[Indexed for MEDLINE]
Free PMC Article

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