Abstract
Oxidative stress plays a crucial role in Alzheimer’s disease (AD) from its prodromal stage of mild cognitive impairment. There is an interplay between oxidative stress and the amyloid β (Aβ) cascade via various mechanisms including mitochondrial dysfunction, lipid peroxidation, protein oxidation, glycoxidation, deoxyribonucleotide acid damage, altered antioxidant defense, impaired amyloid clearance, inflammation and chronic cerebral hypoperfusion. Based on findings that indicate that oxidative stress plays a major role in AD, oxidative stress has been considered as a therapeutic target of AD. In spite of favorable preclinical study outcomes, previous antioxidative components, including a single antioxidative supplement such as vitamin C, vitamin E or their mixtures, did not clearly show any therapeutic effect on cognitive decline in AD. However, novel antioxidative supplements can be beneficial for AD patients. In this review, we summarize the interplay between oxidative stress and the Aβ cascade, and introduce novel antioxidative supplements expected to prevent cognitive decline in AD.
Highlights
The number of dementia patients is rapidly increasing in aging societies
Alzheimer’s disease (AD) is pathologically characterized by the presence of hallmark lesions such as neuronal loss, and senile plaque consisting of amyloid β (Aβ) and neurofibrillary tangles (NFT)
Peroxidation of membrane lipids affects a variety of functions resulting in increased rigidity, decreased activity of membrane-bound enzymes, impairment of membrane receptors and altered permeability. 4-HNE binds to both nicastrin and beta-site amyloid precursor protein cleaving enzyme (BACE), differentially affecting γ- and β-secretase activity, suggesting that this naturally occurring product of lipid peroxidation may trigger the generation of toxic Aβ species [17]
Summary
The number of dementia patients is rapidly increasing in aging societies. Over 46 million people lived with dementia worldwide in 2015, and this number is estimated to increase to 131.5 million by 2050 [1]. Aβ is rapidly degraded or removed in normal subjects, under pathological conditions, Aβ peptides can accumulate to produce Aβ oligomers, protofibrils or fibrils [3]. In familial cases of early-onset AD, autosomal dominant mutations of APP, PSEN1 and PSEN2 have been identified, and the global prevalence for autosomal dominant forms of early-onset AD is 5–10% [7]. These mutations lead to the accumulation of Aβ and subsequent development of AD. Among non-genetic factors, cerebrovascular disease, hypertension, diabetes mellitus, both low and high body weight, dyslipidemia, metabolic syndrome, smoking and traumatic brain injury increase the risk of AD [10]
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