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SILK studies — capturing the turnover of proteins linked to neurodegenerative diseases

Journal article
Authors R. W. Paterson
A. Gabelle
B. P. Lucey
N. R. Barthélemy
C. A. Leckey
C. Hirtz
S. Lehmann
C. Sato
B. W. Patterson
T. West
K. Yarasheski
J. D. Rohrer
N. C. Wildburger
J. M. Schott
C. M. Karch
S. Wray
T. M. Miller
D. L. Elbert
Henrik Zetterberg
N. C. Fox
R. J. Bateman
Published in Nature Reviews Neurology
Volume 15
Issue 7
Pages 419-427
ISSN 1759-4758
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Pages 419-427
Language en
Links dx.doi.org/10.1038/s41582-019-0222-...
Subject categories Neurosciences

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. © 2019, Springer Nature Limited.

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