Oxidative stress and mitochondrial disturbances are the common and important causative
factors of aging, and play an important role in the late onset of sporadic neurodegenerative diseases,
including Alzheimer disease (AD). Furthermore, emerging evidence from in vitro and in vivo disease models suggests that
oxidative stress and increased vulnerability to induction of mitochondrial permeability transition leads to the pathogenesis
of the neurological disorders. Towards the goals of developing effective neuroprotectors, this article describes the
synthesis and neuroprotective studies of various derivatives of the naturally occurring alkaloid securinine, based on which
a lead compound, allomargaritarine (a diastereomer of margaritarine), was identified as an effective therapeutic for
neuroprotection. Allomargaritarine exhibits high antioxidant activity, and has significant mitoprotective effect on cellular
models of neurodegeneration.
Keywords: Neurodegenerative diseases, neuroprotection, mitochondria, lipid peroxidation, antioxidant, alkaloids, lactones.
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