Lipid peroxidation products and their role in neurodegenerative diseases

Orjona V. Taso, Anastassios Philippou, Athanasios Moustogiannis, Evangelos Zevolis, Michael Koutsilieris


The central nervous system (CNS) is one of the most metabolically active organs and is characterized by elevated oxygen requirements, while it possesses a diminished anti-oxidative action. This can result in impairment in susceptible glia and neurons, due to the production of reactive oxygen species (ROS), and ultimately neurodegeneration. Indeed, oxidative stress is a key component of the pathophysiological mechanisms in a plethora of diseases, including neurodegenerative disorders. Iron, is additionally involved in oxygen transportation and misregulation of iron can cause neurotoxicity through different mechanisms leading to oxidative damage and cell death. Recent discoveries showing that ROS are capable of commencing lipid peroxidation (LPO), a process in which oxidants assault lipids that contain C-C double bonds and particularly polyunsaturated fatty acids (PUFAs). LPO results in the generation of toxic lipid aldehyde species, including 4-hydroxy-2-nonenal (HNE), malondialdehyde, and acrolein. These reactive aldehyde species are generated within enzymatic pathways that lead to post-transcriptional alterations of DNA and proteins, eventually resulting in genotoxicity, inhibition of gene expression, cytotoxicity and cellular death. Among those various molecules, isoprostanes and neuroprostanes are potential key biomarkers for oxidative stress status in neurological disorders. The aim of this review was to describe LPO process and its products, and to characterize their role as potential biomarkers in neurodegenerative diseases (NDs).