English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

The cyanobacterial β-N-methylamino-L-alanine (L-BMAA) is described as a low-potency excitotoxin, possibly a factor in the increased incidence of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) in Guam. The latter association is intensively disputed, as L-BMAA concentrations required for toxic effects exceed those assumed to occur via food. The question thus was raised whether L-BMAA leads to neurodegeneration at nonexcitotoxic conditions. Using human SH-SY5Y neuroblastoma cells, L-BMAA-transport, incorporation into proteins, and subsequent impairment of cellular protein homeostasis were investigated. Binding of L-BMAA to intracellular proteins, but no clear protein incorporation was detected in response to (14)C-L-BMAA exposures. Nevertheless, low L-BMAA concentrations (≥ 0.1mM, 48 h) increased protein ubiquitination, 20S proteasomal and caspase 12 activity, expression of the endoplasmic reticulum (ER) stress marker CHOP, and enhanced phosphorylation of elf2α in SH-SY5Y cells. In contrast, high L-BMAA concentrations (≥ 1mM, 48 h) increased reactive oxygen species and protein oxidization, which were partially ameliorated by coincubation with vitamin E. L-BMAA-mediated cytotoxicity was observable 48 h following ≥ 2mM L-BMAA treatment. Consequently, the data presented here suggest that low L-BMAA concentrations result in a dysregulation of the cellular protein homeostasis with ensuing ER stress that is independent from high-concentration effects such as excitotoxicity and oxidative stress. Thus, the latter could be a contributing factor in the onset and slow progression of ALS/PDC in Guam.

L-BMAA Induced ER Stress and Enhanced Caspase 12 Cleavage in Human Neuroblastoma SH-SY5Y Cells at Low Nonexcitotoxic Concentrations