Premium
Neuroprotectin D1 exerts potent anti‐apoptotic and anti‐amyloidogenic effects in human neural cell models of Alzheimer's disease
Author(s) -
ZHAO YUHAI,
LUKIW WALTER J,
BAZAN NICOLAS G
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.926.4
Subject(s) - neuroprotection , amyloid precursor protein , apoptosis , neurodegeneration , chemistry , amyloid beta , tunel assay , pharmacology , amyloid (mycology) , microbiology and biotechnology , alzheimer's disease , biochemistry , biology , peptide , medicine , disease , inorganic chemistry
The 42 amino acid amyloid‐ ? (A ?42) peptide is widely considered as a key molecule implicated in pathogenesis of Alzheimer's disease (AD). Recent studies suggest that neuroprotectin D1 (NPD1), an enzymatic metabolite of docosahexaenoic acid (DHA), may help counteract pathological changes occurring in neurodegenerative disorders such as AD. In this study we sought to investigate the mechanism of NPD1's neuroprotective actions and effects on beta amyloid precursor protein ( ?APP) processing. In a cellular model of AD involving A ?42‐stressed human neural (HN) cells in primary culture, NPD1 significantly ameliorated A ?42‐induced cell death and apoptosis as measured by MTT, caspase‐3 assay, TUNEL and Hoechst 33258 staining. A ?42‐induced expression of the pro‐inflammatory cyclooxygenase‐2 (COX‐2) and cytokine tumor necrosis factor a (TNF‐a) were also reduced by NPD1. In HN cells over‐expressing ?APP, NPD1 significantly suppressed A ? peptide release while the generation of neurotrophic sΑPPα peptides was elevated. Our most recent data suggest that peroxisomal proliferator‐activated receptor ? (PPAR?) might be implicated in the neuroprotective actions of NPD1. In conclusion, NPD1 demonstrated potent anti‐apoptotic, anti‐inflammatory and anti‐amyloidogenic effects in HN cell models of AD, in part, via the targeting of PPAR? and the α‐ and β‐secretase systems.