Neuronal proteostasis is uniquely challenged by the extraordinary architecture of neurons, the vast number of synapses they form, and the need to precisely preserve function at individual synapses. Quantitative information on protein lifetimes can provide clues as to how these challenges are met. Advances in proteomics and mass spectrometry, which now enable comprehensive lifetime estimations for thousands of proteins, suggest that neuronal and synaptic protein lifetimes are unusually long, with half-lives typically ranging from days to weeks, even months and beyond for certain protein families. Half-lives in vivo are several-fold longer than those in cell culture, tend to cluster for proteins belonging to multimolecular complexes, are affected by developmental stage, and possibly by environmental conditions and activity levels.
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