Lipid Peroxidation and Antioxidant Supplementation in Neurodegenerative Diseases: A Review of Human Studies

Abstract

Being characterized by progressive and severe damage in neuronal cells, neurodegenerative diseases (NDDs) are the major cause of disability and morbidity in the elderly, imposing a significant economic and social burden. As major components of the central nervous system, lipids play important roles in neural health and pathology. Disturbed lipid metabolism, particularly lipid peroxidation (LPO), is associated with the development of many NDDs, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), all of which show elevated levels of LPO products and LPO-modified proteins. Thus, the inhibition of neuronal oxidation might slow the progression and reduce the severity of NDD; natural antioxidants, such as polyphenols and antioxidant vitamins, seem to be the most promising agents. Here, we summarize current literature data that were derived from human studies on the effect of natural polyphenols and vitamins A, C, and E supplementation in patients with AD, PD, and ALS. Although these compounds may reduce the severity and slow the progression of NDD, research gaps remain in antioxidants supplementation in AD, PD, and ALS patients, which indicates that further human studies applying antioxidant supplementation in different forms of NDDs are urgently needed.

Narrative Review of n-3 Polyunsaturated Fatty Acid Supplementation upon Immune Functions, Resolution Molecules and Lipid Peroxidation

“…Oxidation of lipids, proteins, or nucleic acids can be assessed using tests for specific oxidation products [ 89 , 90 , 91 , 92 , 93 ]. For example, F3-isoprostanes represent oxidation of EPA [ 92 ].…”

“…For example, F3-isoprostanes represent oxidation of EPA [ 92 ]. F2-isoprostanes represent oxidation derived from arachidonic acid, and F4-neuroprostanes derive from oxidation of DHA [ 90 , 91 , 92 , 93 ]. In addition, the aldehydes 4-hydroxynonenal (HNE) derive from n -6 PUFA oxidation while 4-hydroxyhexenal (HHE) derive from n -3 PUFA oxidation [ 93 ].…”

“…F2-isoprostanes represent oxidation derived from arachidonic acid, and F4-neuroprostanes derive from oxidation of DHA [ 90 , 91 , 92 , 93 ]. In addition, the aldehydes 4-hydroxynonenal (HNE) derive from n -6 PUFA oxidation while 4-hydroxyhexenal (HHE) derive from n -3 PUFA oxidation [ 93 ]. There are also specific oxidation products that derive from protein and nucleic acid oxidation [ 89 ].…”

N-3 PUFA Prevent Oxidative Stress in a Rat Model of Beta-Amyloid-Induced Toxicity

“…Among the components of the antioxidant system, superoxide dismutase 1 (SOD1) enzyme, and reduced glutathione (GSH) have been described to play a crucial role in CNS protection against oxidative damage [ 20 , 21 ]. Preclinical and clinical reports have pointed towards a crucial role of n-3 PUFA in preventing dysfunctions of antioxidant pathways observed in neurodegenerative disorders [ 22 , 23 ]. Nonetheless, increased production of reactive species, by inducing an altered intracellular signaling, has also been linked to dysregulation of the inflammatory response.…”

Lipid Peroxidation in Neurodegeneration

“…In this sense, the inhibition of neuronal oxidation could avoid disease progression, as well as reducing its severity. A review of promising antioxidant agents (polyphenols, antioxidant vitamins…) was carried out, showing some potential benefits of antioxidant supplementation [ 1 ].…”