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Ferulic acid ethyl ester protects neurons against amyloid β‐ peptide(1–42)‐induced oxidative stress and neurotoxicity: relationship to antioxidant activity
Author(s) -
Sultana Rukhsana,
Ravagna Agrippino,
MohmmadAbdul Hafiz,
Calabrese Vittorio,
Butterfield D. Allan
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02899.x
Subject(s) - neurotoxicity , oxidative stress , ferulic acid , antioxidant , chemistry , peptide , amyloid β , oxidative damage , biochemistry , amyloid (mycology) , pharmacology , toxicity , medicine , organic chemistry , disease , inorganic chemistry
Alzheimer's disease (AD) is neuropathologically characterized by depositions of extracellular amyloid and intracellular neurofibrillary tangles, associated with loss of neurons in the brain. Amyloid β‐peptide (Aβ) is the major component of senile plaques and is considered to have a causal role in the development and progress of AD. Several lines of evidence suggest that enhanced oxidative stress and inflammation play important roles in the pathogenesis or progression of AD. The present study aimed to investigate the protective effects of ethyl‐4‐hydroxy‐3‐methoxycinnamic acid (FAEE), a phenolic compound which shows antioxidant and anti‐inflammatory activity, on Aβ(1–42)‐induced oxidative stress and neurotoxicity. We hypothesized that the structure of FAEE would facilitate radical scavenging and may induce protective proteins. Aβ(1–42) decreases cell viability, which was correlated with increased free radical formation, protein oxidation (protein carbonyl, 3‐nitrotyrosine), lipid peroxidation (4‐hydroxy‐2‐ trans ‐nonenal) and inducible nitric oxide synthase. Pre‐treatment of primary hippocampal cultures with FAEE significantly attenuated Aβ(1–42)‐induced cytotoxicity, intracellular reactive oxygen species accumulation, protein oxidation, lipid peroxidation and induction of inducible nitric oxide synthase. Treatment of neurons with Aβ(1–42) increases levels of heme oxygenase‐1 and heat shock protein 72. Consistent with a cellular stress response to the Aβ(1–42)‐induced oxidative stress, FAEE treatment increases the levels of heme oxygenase‐1 and heat shock protein 72, which may be regulated by oxidative stresses in a coordinated manner and play a pivotal role in the cytoprotection of neuronal cells against Aβ(1–42)‐induced toxicity. These results suggest that FAEE exerts protective effects against Aβ(1–42) toxicity by modulating oxidative stress directly and by inducing protective genes. These findings suggest that FAEE could potentially be of importance for the treatment of AD and other oxidative stress‐related diseases.