Record Detail

The unfolded protein response (UPR) is a high-
ly evolutionarily conserved response to endoplasmic retic-
ulum (ER) stress, which functions to return cells to ho-
meostasis or send them into apoptosis, depending on the
degree of cellular damage. β-N-methylamino- L -alanine
( L -BMAA) has been shown to induce ER stress in a vari-
ety of models and has been linked to several types of
neurodegenerative disease including Guamanian amyotro-
phic lateral sclerosis/Parkinsonism dementia complex
(ALS/PDC). L -Serine, an amino acid critical for cellular
metabolism and neurological signaling, has been shown to
be protective against L -BMAA-induced neurotoxicity in
both animal and cell culture models. While the mecha-
nisms of L -BMAA neurotoxicity have been well charac-
terized, less is known about L -serine neuroprotection. We
recently reported that L -serine and L -BMAA generate sim-
ilar differential expression profiles in a human ER stress/
UPR array, despite L -serine being neuroprotective and L-
BMAA being linked to neurodegenerative disease. Here,
we further investigate the mechanism(s) of L -serine-in-
duced UPR dysregulation by examining key genes and
proteins in the ER stress/UPR pathways. We report that
L -serine selectively increased protein disulfide isomerase
(PDI) protein translation, an ER chaperone involved in
refolding misfolded proteins, suggesting it may be