Suppression of tau‐induced phenotypes by vitamin E demonstrates the dissociation of oxidative stress and phosphorylation in mechanisms of tau toxicity

Cowan, Catherine M.; Sealey, Megan; Mudher, Amritpal

doi:10.1111/jnc.15253

Cited by 15 publications

(6 citation statements)

References 54 publications

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“…Vulnerability to oxidative stress has been employed as a measure of tau accumulation-dependent toxicity in tauopathies including Alzheimer’s disease [ 44 , 45 ] and has been modeled in Drosophila [ 32 , 33 , 46 , 47 ]. Hence, the resistance of adult hTau expressing flies and controls to 5% H 2 O 2 was assessed as before [ 32 , 33 , 48 ].…”

Section: Resultsmentioning

confidence: 99%

Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS

Vourkou

Paspaliaris

Bourouliti

et al. 2022

IJMS

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Accumulation of highly post-translationally modified tau proteins is a hallmark of neurodegenerative disorders known as tauopathies, the most common of which is Alzheimer’s disease. Although six tau isoforms are found in the human brain, the majority of animal and cellular tauopathy models utilize a representative single isoform. However, the six human tau isoforms present overlapping but distinct distributions in the brain and are differentially involved in particular tauopathies. These observations support the notion that tau isoforms possess distinct functional properties important for both physiology and pathology. To address this hypothesis, the six human brain tau isoforms were expressed singly in the Drosophila brain and their effects in an established battery of assays measuring neuronal dysfunction, vulnerability to oxidative stress and life span were systematically assessed comparatively. The results reveal isoform-specific effects clearly not attributed to differences in expression levels but correlated with the number of microtubule-binding repeats and the accumulation of a particular isoform in support of the functional differentiation of these tau isoforms. Delineation of isoform-specific effects is essential to understand the apparent differential involvement of each tau isoform in tauopathies and their contribution to neuronal dysfunction and toxicity.

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Section: Resultsmentioning

confidence: 99%

Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS

Vourkou

Paspaliaris

Bourouliti

et al. 2022

IJMS

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show abstract

“…Additionally, in another meta-analysis, it has been reported that a low concentration of serum vitamin E is associated with AD [ 105 ]. Moreover, substantial evidence suggested that vitamin E successfully suppresses tau-induced neurotoxicity in Drosophila [ 106 , 107 , 108 ]. In one of the recent studies, it is proposed that vitamin E has significantly reduced oxidative and nitrosative damage in AD [ 109 ].…”

Section: Role Of Antioxidants In Alzheimer’s Diseasementioning

confidence: 99%

Antioxidants in Alzheimer’s Disease: Current Therapeutic Significance and Future Prospects

Pritam

Deka

Bhardwaj

et al. 2022

Biology

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Alzheimer’s disease (AD) rate is accelerating with the increasing aging of the world’s population. The World Health Organization (WHO) stated AD as a global health priority. According to the WHO report, around 82 million people in 2030 and 152 million in 2050 will develop dementia (AD contributes 60% to 70% of cases), considering the current scenario. AD is the most common neurodegenerative disease, intensifying impairments in cognition, behavior, and memory. Histopathological AD variations include extracellular senile plaques’ formation, tangling of intracellular neurofibrils, and synaptic and neuronal loss in the brain. Multiple evidence directly indicates that oxidative stress participates in an early phase of AD before cytopathology. Moreover, oxidative stress is induced by almost all misfolded protein lumps like α-synuclein, amyloid-β, and others. Oxidative stress plays a crucial role in activating and causing various cell signaling pathways that result in lesion formations of toxic substances, which foster the development of the disease. Antioxidants are widely preferred to combat oxidative stress, and those derived from natural sources, which are often incorporated into dietary habits, can play an important role in delaying the onset as well as reducing the progression of AD. However, this approach has not been extensively explored yet. Moreover, there has been growing evidence that a combination of antioxidants in conjugation with a nutrient-rich diet might be more effective in tackling AD pathogenesis. Thus, considering the above-stated fact, this comprehensive review aims to elaborate the basics of AD and antioxidants, including the vitality of antioxidants in AD. Moreover, this review may help researchers to develop effectively and potentially improved antioxidant therapeutic strategies for this disease as it also deals with the clinical trials in the stated field.

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“…For instance, in AD-like models based on metabolic dysfunction and redox imbalance, L-carnitine has been shown to exert neuroprotective effects through mechanisms involving both the enhancement of cell metabolism and the improvement of antioxidant defenses [ 203 ]. Likewise, since reduced concentrations of different forms of vitamin E have been observed in AD patients compared to healthy controls [ 204 ], treatments with vitamin E have been considered to overcome oxidative damage and neuronal degeneration [ 205 , 206 , 207 ], and to reduce the risk of developing AD [ 208 , 209 ]. However, most of the clinical trials examining the efficacy of vitamin E treatment have yielded uncertain results in delaying or halting the onset and the progression of AD [ 210 , 211 , 212 , 213 ].…”

Section: Ros and Antioxidants In Neurodegenerative Diseasesmentioning

confidence: 99%

The Hidden Notes of Redox Balance in Neurodegenerative Diseases

et al. 2022

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Reactive oxygen species (ROS) are versatile molecules that, even if produced in the background of many biological processes and responses, possess pleiotropic roles categorized in two interactive yet opposite domains. In particular, ROS can either function as signaling molecules that shape physiological cell functions, or act as deleterious end products of unbalanced redox reactions. Indeed, cellular redox status needs to be tightly regulated to ensure proper cellular functioning, and either excessive ROS accumulation or the dysfunction of antioxidant systems can perturb the redox homeostasis, leading to supraphysiological concentrations of ROS and potentially harmful outcomes. Therefore, whether ROS would act as signaling molecules or as detrimental factors strictly relies on a dynamic equilibrium between free radical production and scavenging resources. Of notice, the mammalian brain is particularly vulnerable to ROS-mediated toxicity, because it possesses relatively poor antioxidant defenses to cope with the redox burden imposed by the elevated oxygen consumption rate and metabolic activity. Many features of neurodegenerative diseases can in fact be traced back to causes of oxidative stress, which may influence both the onset and progression of brain demise. This review focuses on the description of the dual roles of ROS as double-edge sword in both physiological and pathological settings, with reference to Alzheimer’s and Parkinson’s diseases.

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Suppression of tau‐induced phenotypes by vitamin E demonstrates the dissociation of oxidative stress and phosphorylation in mechanisms of tau toxicity

Cited by 15 publications

References 54 publications

Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS

Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS

Antioxidants in Alzheimer’s Disease: Current Therapeutic Significance and Future Prospects

The Hidden Notes of Redox Balance in Neurodegenerative Diseases

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