Nordihydroguaiaretic acid protects hippocampal neurons against amyloid beta-peptide toxicity, and attenuates free radical and calcium accumulation.

TitleNordihydroguaiaretic acid protects hippocampal neurons against amyloid beta-peptide toxicity, and attenuates free radical and calcium accumulation.
Publication TypeJournal Article
Year of Publication1994
JournalBrain research
Volume654
Issue1
Pagination171-6
Date Published1994
ISSN0006-8993
Abstract

Recent findings indicate that amyloid beta-peptide (A beta) can be neurotoxic by a mechanism involving an increase in the concentration of intracellular free Ca2+ ([Ca2+]i) and the generation of free radicals. In the present study, the lipoxygenase inhibitor/antioxidant nordihydroguaiaretic acid (NDGA) protected cultured rat hippocampal neurons against the toxicity of A beta in a concentration-dependent manner. Measurements of cellular oxidation (using the oxidation-sensitive dye 2,7-dichlorofluorescin) and intracellular free Ca2+ levels (using the Ca2+ indicator dye fura-2), showed that NDGA suppressed A beta-induced accumulation of reactive oxygen species (ROS) and Ca2+; Ca2+ responses to glutamate were also suppressed by NDGA. NDGA prevented neuronal injury and accumulation of ROS induced by iron, indicating a role for NDGA as an antioxidant in NDGA-mediated neuroprotection. Another lipoxygenase inhibitor (AA861) also protected against A beta and iron toxicity whereas the the 5-lipoxygenase-activating protein inhibitor L655,238 and the cyclooxygenase inhibitor indomethacin were ineffective. These findings suggest that NDGA can interupt a neurodegenerative pathway relevant to the pathophysiology of Alzheimer's disease.

URLhttps://linkinghub.elsevier.com/retrieve/pii/0006-8993(94)91586-5
Short TitleBrain Res
X
Enter your linkblue username.
Enter your linkblue password.
Secure Login

This login is SSL protected

Loading