UPA Perpustakaan Universitas Jember

Mechanisms of L -Serine Neuroprotection in vitro Include ER Proteostasis Regulation

R. A. Dunlop 1,2 - Personal Name
G. J. Guillemin 2 - Personal Name
P. A. Cox 1 - Personal Name
J. Powell 1 - Personal Name

β-N-methylamino- L -alanine (L-BMAA) is a neu-
rotoxic 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 con-
taminated with L -BMAA. However, the addition of the natu-
rally occurring amino acid L -serine to the diet of the nonhu-
man 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 im-
part 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 incor-
poration of L -BMAA into proteins hence preventing
proteotoxic stress. However, there are likely other mecha-
nisms for L -serine-mediated neuroprotection. Here, we ex-
plore 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 west-
ern 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

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Unfolded protein response
Neuroprotection
ER stress
L -Serine
L -BMAA

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Mechanisms of L -Serine Neuroprotection in vitro Include ER Proteostasis Regulation

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NPP. 3509212D1000001

Mechanisms of L -Serine Neuroprotection in vitro Include ER Proteostasis Regulation

R. A. Dunlop 1,2 - Personal NameG. J. Guillemin 2 - Personal NameP. A. Cox 1 - Personal NameJ. Powell 1 - Personal Name

Series Title

Call Number

Publisher

Collation

Language

ISBN/ISSN

Classification

Content Type

Media Type

Carrier Type

Edition

Subject(s)

Specific Detail Info

Statement of Responsibility

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R. A. Dunlop 1,2 - Personal Name
G. J. Guillemin 2 - Personal Name
P. A. Cox 1 - Personal Name
J. Powell 1 - Personal Name