Selenium attenuates A beta production and A beta-induced neuronal death.
The objective of the present study was to examine the role of selenium in the metabolism of A beta and in A beta-induced neuronal death. Selenium treatment significantly reduced A beta 40, A beta 42, and sAPP beta production by reducing A beta producing beta-secretase and gamma-secretase activities. The lipid peroxidation product 4-Hydroxynonenal (HNE)-induced transcription of beta-secretase (BACE1) was blocked by selenium. Finally, our data show that selenium protects against HNE and A beta-mediated toxicity in primary cultured neurons. The present study suggests that selenium may be able to salvage the neuronal degeneration of Alzheimer's disease, thereby limiting beta-amyloid production and neuronal death.
Gwon
A-Ryeong
AR
College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Suwon 440-746, Republic of Korea.
Park
Jong-Sung
JS
Park
Jun-Hyung
JH
Baik
Sang-Ha
SH
Jeong
Hye-Young
HY
Hyun
Dong-Hoon
DH
Park
Kye Won
KW
Jo
Dong-Gyu
DG
D000447:Aldehydes / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D012643:Selenium / Q000494:pharmacology*
D000447:Aldehydes; D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D053829:Amyloid Precursor Protein Secretases; D012643:Selenium; C027576:4-hydroxy-2-nonenal