NDLI: Mechanisms of l-Serine Neuroprotection in vitro Include ER Proteostasis Regulation

Content Provider	Springer Nature Link
Author	Dunlop, R. A. Powell, J. Guillemin, G. J. Cox, P. A.
Copyright Year	2017
Abstract	β-N-methylamino-l-alanine (L-BMAA) is a neurotoxic non-protein amino acid produced by cyanobacteria. Recently, chronic dietary exposure to l-BMAA was shown to trigger neuropathology in nonhuman primates consistent with Guamanian ALS/PDC, a paralytic disease that afflicts Chamorro villagers who consume traditional food items contaminated with l-BMAA. However, the addition of the naturally occurring amino acid l-serine to the diet of the nonhuman primates resulted in a significant reduction in ALS/PDC neuropathology. l-serine is a dietary amino acid that plays a crucial role in central nervous system development, neuronal signaling, and synaptic plasticity and has been shown to impart neuroprotection from l-BMAA-induced neurotoxicity both in vitro and in vivo. We have previously shown that l-serine prevents the formation of autofluorescent aggregates and death by apoptosis in human cell lines and primary cells. These effects are likely imparted by l-serine blocking incorporation of l-BMAA into proteins hence preventing proteotoxic stress. However, there are likely other mechanisms for l-serine-mediated neuroprotection. Here, we explore the molecular mechanisms of l-serine neuroprotection using a human unfolded protein response real-time PCR array with genes from the ER stress and UPR pathways, and western blotting. We report that l-serine caused the differential expression of many of the same genes as l-BMAA, even though concentrations of l-serine in the culture medium were ten times lower than that of l-BMAA. We propose that l-serine may be functioning as a small proteostasis regulator, in effect altering the cells to quickly respond to a possible oxidative insult, thus favoring a return to homeostasis.
Starting Page	123
Ending Page	132
Page Count	10
File Format	PDF
ISSN	10298428
Journal	Neurotoxicity Research
Volume Number	33
Issue Number	1
e-ISSN	14763524
Language	English
Publisher	Springer US
Publisher Date	2017-11-02
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Unfolded protein response ER stress Neuroprotection l-serine l-BMAA Neurosciences Neurology Neurochemistry Pharmacology/Toxicology Neurobiology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Toxicology

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