Modification of ion homeostasis by lipid peroxidation: roles in neuronal degeneration and adaptive plasticity

Oxyradicals attack double bonds of unsaturated fatty acids in cell membranes in a process called membrane lipid peroxidation (MLP). This process occurs in many different acute and chronic neurodegenerative conditions, and to a lesser extent during normal physiological activity in neuronal circuits. It can modify neurotransmitter release and uptake, ion-channel activity, the function of ion-motive ATPases and glucose transporters, and the coupling of cell-surface receptors to GTP-binding proteins. MLP can also impair mitochondrial function and promote a cascade of events that culminates in apoptotic cell death. The lipid peroxidation product 4-hydroxynonenal might play a central role in MLP-induced alterations in plasma membrane and mitochondrial protein functions. The modification of processes such as outgrowth of neurites and long-term potentiation of synaptic transmission by agents that suppress or promote MLP suggests roles for subtoxic levels of MLP in neuronal plasticity.