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• W2949287877 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. Paterson and colleagues describe how stable isotope labelling kinetics (SILK) can be used to determine protein production and clearance rates. They highlight the promise of SILK studies for elucidating the role of pathogenic proteins in neurodegenerative diseases, including Alzheimer disease." @default.
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• W2949287877 date "2019-06-20" @default.
• W2949287877 modified "2023-10-17" @default.
• W2949287877 title "SILK studies — capturing the turnover of proteins linked to neurodegenerative diseases" @default.
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• W2949287877 doi "https://doi.org/10.1038/s41582-019-0222-0" @default.
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