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

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Lipid Peroxidation and Antioxidant Supplementation in Neurodegenerative Diseases: a Review of Human Studies antioxidants Review Lipid Peroxidation and Antioxidant Supplementation in Neurodegenerative Diseases: A Review of Human Studies Snjezana Petrovic 1 , Aleksandra Arsic 1, Danijela Ristic-Medic 1 , Zorica Cvetkovic 2,3 and Vesna Vucic 1,* 1 Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia; [email protected] (S.P.); [email protected] (A.A.); [email protected] (D.R.-M.) 2 Department of Hematology, Clinical Hospital Center Zemun, 11000 Belgrade, Serbia; [email protected] 3 Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia * Correspondence: [email protected] or [email protected]; Tel.: +381-11-303-1997 Received: 29 September 2020; Accepted: 30 October 2020; Published: 13 November 2020 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. Keywords: neurodegenerative diseases; lipid peroxidation; antioxidant supplementation; Alzheimer’s disease; Parkinson’s disease; amyotrophic lateral sclerosis 1. Introduction Neurodegenerative diseases (NDDs) have become the major cause of disability and morbidity among older people worldwide due to the ageing society and the increased average life expectancy. Suffering from severe memory and behavioral impairment (dementia) and the loss of movement control (ataxia and paralysis), these patients need constant and long-term care, which is connected with huge economic and societal costs. Neurodegenerative diseases is a collective term for the clinical conditions characterized by gradual and progressive severe damage to neuronal cells, particularly in the central nervous system (CNS), which results in the loss of functions that are associated with the affected brain region [1,2]. Different in etiology and clinical symptomatology, NDDs share some common features at the cellular and molecular levels, such as protein misfolding, aggregation, and deposition; mitochondrial disfunction; chronic inflammation; and, oxidative damage of biomolecules, including lipids, proteins, and DNA (Figure1). Antioxidants 2020, 9, 1128; doi:10.3390/antiox9111128 www.mdpi.com/journal/antioxidants Antioxidants 2020, 9, x FOR PEER REVIEW 2 of 29 and molecular levels, such as protein misfolding, aggregation, and deposition; mitochondrial disfunction;Antioxidants 2020 chronic, 9, 1128 inflammation; and, oxidative damage of biomolecules, including lipids, proteins,2 of 27 and DNA (Figure 1). The most common type of NDD is Alzheimer’s disease (AD), accounting for approximately two-thirds of all cases [3]. Other NDDs include Parkinson’s disease (PD), Huntington’sThe most common disease, type multiple of NDD sclerosis, is Alzheimer’s amyotrophic disease (AD),lateral accounting sclerosis (ALS), for approximately and many other two-thirds rare conditions,of all cases [such3]. Other as: prion NDDs diseases, include Parkinson’smotor neuron disease diseases, (PD), spinocerebellar Huntington’s disease, ataxia, multiplespinal muscular sclerosis, atrophy,amyotrophic Friedreich’s lateral sclerosis ataxia, (ALS),and Lewy and manybody otherdisease. rare All conditions, of these suchdiseases, as: prion whether diseases, genetic motor or acquired,neuron diseases, lead to spinocerebellarthe progressive ataxia,decline spinal or even muscular the complete atrophy, loss Friedreich’s of sensory, ataxia, motor, and and Lewy cognitive body function.disease. AllAD, of PD, these and diseases, ALS are whether typically genetic found or acquired,in the elderly lead to and the progressiveare primarily decline classified or even as proteinopathies,the complete loss meaning of sensory, that motor,they are and associated cognitive with function. the aggregation AD, PD, andand ALSdeposition are typically of misfolded found proteinsin the elderly that trigger and are neurotoxicity primarily classified through as cellular proteinopathies, stress pathways meaning [4,5]. that In they ALS, are both associated upper withand lowerthe aggregation motor neurons and are deposition affected of[6]. misfolded The disruption proteins of proteostasis that trigger (protein neurotoxicity homeostasis) through can cellular occur atstress any pathwaysstep of protein [4,5]. Insynthesis, ALS, both including upper and during lower transcription, motor neurons translation, are affected and [ 6post-translational]. The disruption modification.of proteostasis (protein homeostasis) can occur at any step of protein synthesis, including during transcription, translation, and post-translational modification. Figure 1. Pathophysiological mechanisms of Alzheimer’s disease (AD), Parkinson’s disease (PD), Figureand amyotrophic 1. Pathophysiological lateral sclerosis mechanisms (ALS) development of Alzheimer’ ands disease progression. (AD), ReactiveParkinson’s oxygen disease species (PD), (ROS) and amyotrophicproduced by mitochondriallateral sclerosis Cyt (ALS) p-450, development nicotinamide and adenine progression. dinucleotide Reactive phosphate oxygen (NADPH) species oxidase, (ROS) producedand lipoxygenase by mitochondrial (LOX) attacks Cyt brainp-450, lipids, nicotina proteins,mide andadenine DNA, dinucleotide further increasing phosphate oxidative (NADPH) stress. oxidase,Oxidative and damage lipoxygenase of lipids (LOX) results attacks in the formationbrain lipids, of proteins, lipid peroxidation and DNA, (LPO) further products, increasing which oxidative further stress.attack lipids,Oxidative proteins, damage and of DNA, lipids impairing results in brain the function.formation LPO of lipid can a ffperoxidationect different types(LPO) ofproducts, neurons: whichin hippocampal further attack neurons, lipids, LPO proteins, products and bind DNA, to amyloidimpairingβ brainpeptide function. and form LPO misfolded can affect amyloid differentβ typespeptide of andneurons: amyloid in βhippocampalsenile plaque, neur whichons, disturbsLPO products nerve signaling bind to andamyloid structure β peptide and induces and form AD; misfoldedin dopaminergic amyloid neurons, β peptide LPO productsand amyloid induce β generationsenile plaque, and accumulationwhich disturbs of misfoldednerve signalingα-synuclein, and structureresulting inand insu inducesfficient dopamineAD; in dopaminergic production and ne developmenturons, LPO products of PD; in motorinduce neurons, generation mutation and accumulationof the superoxide of dismutasemisfolded 1α(SOD1)-synuclein,gene leadsresulting to the in formation insufficient of misfoldeddopamine SOD1 production enzymes and and developmentabnormal production of PD; in ofmotor ROS neurons, and LPO mu products,tation of causing the superoxide necrosis dismutase and death 1 of (SOD1) the affected gene neuronsleads to thein ALS; formation LPO-modified of misfolded proteins SOD1 are enzymes also associated and ab withnormal neural production disruption of ROS in ALS. and AD, LPO Alzheimer’s products, causingdisease; necrosis PD, Parkinson’s and death disease; of the affected ALS, amyotrophic neurons in ALS; lateral LPO-modified sclerosis; ROS, protei reactivens are oxygenalso associated species; withNADPH, neural nicotinamide disruption in adenine ALS. AD, dinucleotide Alzheimer’s phosphate; disease; LOX,PD, Parkinson’s lipoxygenase; disease; LPO, LipidALS, amyotrophic peroxidation; lateralSOD1, superoxidesclerosis; ROS, dismutase reactive 1. oxygen species; NADPH, nicotinamide adenine dinucleotide phosphate; LOX, lipoxygenase; LPO, Lipid peroxidation; SOD1, superoxide dismutase 1. Chaperons, which are proteins that facilitate the formation of correct and stable protein conformations,Chaperons, recognition which are and proteins translocation that facilitate of misfolded the formation proteins into of thecorrect cytosol, and and stable cooperation protein conformations,with the ubiquitin recognition/proteasome and pathwaytranslocation (UPP) of or misf theolded autophagy–lysosome proteins into the pathwaycytosol, and (ALP) cooperation to trigger withdegradation the ubiquitin/proteasome of misfolded proteins, pathway regulate (UPP) proteinor the autophagy–lysosome folding [7,8]. The mammalian pathway (ALP) targets to trigger of the rapamycin (mTOR) and sirtuin (SIRT) signaling pathways are key regulators of clearance mechanisms to prevent accumulation
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