Cell Death via Lipid Peroxidation and Protein Aggregation Diseases

Abstract

Lipid peroxidation of cellular membranes is a complicated cellular event, and it is both the cause and result of various diseases, such as ischemia-reperfusion injury, neurodegenerative diseases, and atherosclerosis. Lipid peroxidation causes non-apoptotic cell death, which is associated with cell fate determination: survival or cell death. During the radical chain reaction of lipid peroxidation, various oxidized lipid products accumulate in cells, followed by organelle dysfunction and the induction of non-apoptotic cell death. Highly reactive oxidized products from unsaturated fatty acids are detected under pathological conditions. Pathological protein aggregation is the general cause of these diseases. The cellular response to misfolded proteins is well-known as the unfolded protein response (UPR) and it is partially concomitant with the response to lipid peroxidation. Moreover, the association between protein aggregation and non-apoptotic cell death by lipid peroxidation is attracting attention. The link between lipid peroxidation and protein aggregation is a matter of concern in biomedical fields. Here, we focus on lethal protein aggregation in non-apoptotic cell death via lipid peroxidation. We reviewed the roles of protein aggregation in the initiation and execution of non-apoptotic cell death. We also considered the relationship between protein aggregation and oxidized lipid production. We provide an overview of non-apoptotic cell death with a focus on lipid peroxidation for therapeutic targeting during protein aggregation diseases.

Cellular senescence, rejuvenation and potential immortality

“…Some of the principal causes of molecular damage in cells are reactive oxygen species (ROS), highly reactive chemicals, such as peroxides, produced as a result of oxidative phosphorylation in mitochondria and other oxidative processes. ROS damage lipids by peroxidation, and proteins by carbonylation, introducing ketone or aldehyde groups into protein sidechains [10,11]. Lower levels of ROS generally lead to less accumulation of age-related damage [12].…”

Engineering Nano‐ and Microparticles as Oral Delivery Vehicles to Promote Intestinal Lymphatic Drug Transport

“…[ 12,40 ] Lipids contain hydrophobic and amphiphilic molecules, including phospholipids, cholesterols, fatty acids, and triglycerides, diglycerides, and monoglycerides ( Figure ). [ 41–44 ] Orally administered dietary lipids are absorbed into the enterocytes and packaged into chylomicrons, which are then transported into the ILS. [ 40,45,46 ]…”

“…[12,40] Lipids contain hydrophobic and amphiphilic molecules, including phospholipids, cholesterols, fatty acids, and triglycerides, diglycerides, and monoglycerides (Figure 2). [41][42][43][44] Orally administered dietary lipids are absorbed into the enterocytes and packaged into chylomicrons, which are then transported into the ILS. [40,45,46] The endogenous lymphatic absorption of dietary lipids has motivated formulation scientists to design sophisticated lipidbased delivery systems that can target enterocytes for lymphatic drug transport.…”

Molecular Mechanisms and Therapeutic Potential of α- and β-Asarone in the Treatment of Neurological Disorders

“…In general, neurological disorders are characterized by acute and progressive neuron degeneration, ultimately resulting in brain dysfunction and neuronal cell death [ 3 ]. The underlying molecular mechanisms of neurodegeneration include alterations in phospholipid metabolism, accumulation of lipid peroxides, mitochondrial dysfunction, protein misfolding, abnormal protein aggregation, diminished cellular energy levels, disturbed calcium (Ca 2+ ) homeostasis, excitotoxicity, oxidative stress, neuroinflammation, dysregulated hormonal signalling, and apoptosis [ 4 , 5 , 6 ].…”