The Role of Dietary Antioxidants and Their Potential Mechanisms in Alzheimer’s Disease Treatment

Knight, Emily; Geetha, Thangiah; Babu, Jeganathan Ramesh

doi:10.3390/metabo13030438

Cited by 9 publications

(2 citation statements)

References 162 publications

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“…Vitamins are extensively examined substances in clinical studies for AD. Their safety and efficacy evaluations commenced in the 1990s and are currently ongoing [242]. High doses of vitamin B (folate 5 mg, vitamin B6 25 mg, and vitamin B12 1 mg) were used in a controlled, randomized trial to assess the safety and effectiveness of B vitamin supplementation in AD.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

A Combinational Therapy for Preventing and Delaying the Onset of Alzheimer’s Disease: A Focus on Probiotic and Vitamin Co-Supplementation

Sultana,

Hia,

Reddy

2024

Antioxidants

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Alzheimer’s disease is a progressive neurodegenerative disorder with a complex etiology, and effective interventions to prevent or delay its onset remain a global health challenge. In recent years, there has been growing interest in the potential role of probiotic and vitamin supplementation as complementary strategies for Alzheimer’s disease prevention. This review paper explores the current scientific literature on the use of probiotics and vitamins, particularly vitamin A, D, E, K, and B-complex vitamins, in the context of Alzheimer’s disease prevention and management. We delve into the mechanisms through which probiotics may modulate gut–brain interactions and neuroinflammation while vitamins play crucial roles in neuronal health and cognitive function. The paper also examines the collective impact of this combinational therapy on reducing the risk factors associated with Alzheimer’s disease, such as oxidative stress, inflammation, and gut dysbiosis. By providing a comprehensive overview of the existing evidence and potential mechanisms, this review aims to shed light on the promise of probiotic and vitamin co-supplementation as a multifaceted approach to combat Alzheimer’s disease, offering insights into possible avenues for future research and clinical application.

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Section: Safety and Tolerabilitymentioning

confidence: 99%

A Combinational Therapy for Preventing and Delaying the Onset of Alzheimer’s Disease: A Focus on Probiotic and Vitamin Co-Supplementation

Sultana,

Hia,

Reddy

2024

Antioxidants

View full text Add to dashboard Cite

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“…Furthermore, astrocytes can undergo various detrimental transformations, resulting in either atrophy and loss of function or reactive astrogliosis with hypertrophy [420]. Although melatonin has been shown to have a beneficial role in different neurodegenerative diseases such as AD [421,422], PD [389,423], MS [424], or ALS [425], less is known of its effects on astrocyte activation. In the rat hippocampus, melatonin has been shown to attenuate synaptic dysfunction and reduce astrogliosis improving the Aβ1-42-induced impairment in spatial learning and memory [426].…”

Section: Melatonin In Astrocyte Activationmentioning

confidence: 99%

Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging

Carretero,

Ramos,

Segura-Chama

et al. 2023

Antioxidants

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The aim of this review is to explore the relationship between melatonin, free radicals, and non-excitatory amino acids, and their role in stroke and aging. Melatonin has garnered significant attention in recent years due to its diverse physiological functions and potential therapeutic benefits by reducing oxidative stress, inflammation, and apoptosis. Melatonin has been found to mitigate ischemic brain damage caused by stroke. By scavenging free radicals and reducing oxidative damage, melatonin may help slow down the aging process and protect against age-related cognitive decline. Additionally, non-excitatory amino acids have been shown to possess neuroprotective properties, including antioxidant and anti-inflammatory in stroke and aging-related conditions. They can attenuate oxidative stress, modulate calcium homeostasis, and inhibit apoptosis, thereby safeguarding neurons against damage induced by stroke and aging processes. The intracellular accumulation of certain non-excitatory amino acids could promote harmful effects during hypoxia-ischemia episodes and thus, the blockade of the amino acid transporters involved in the process could be an alternative therapeutic strategy to reduce ischemic damage. On the other hand, the accumulation of free radicals, specifically mitochondrial reactive oxygen and nitrogen species, accelerates cellular senescence and contributes to age-related decline. Recent research suggests a complex interplay between melatonin, free radicals, and non-excitatory amino acids in stroke and aging. The neuroprotective actions of melatonin and non-excitatory amino acids converge on multiple pathways, including the regulation of calcium homeostasis, modulation of apoptosis, and reduction of inflammation. These mechanisms collectively contribute to the preservation of neuronal integrity and functions, making them promising targets for therapeutic interventions in stroke and age-related disorders.

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Emerging Alzheimer's disease treatment paradigms: A late‐stage clinical trial review

Hlávka,

Kinoshita,

Jeyasingh

et al. 2024

A&D Transl Res & Clin Interv

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INTRODUCTIONWithout disease‐modifying interventions, Medicare and Medicaid spending on Alzheimer's disease (AD) management is expected to reach 637 billion USD annually by 2050. The recent advent of promising AD therapies after decades of a near‐total failure rate in clinical trials suggests that more disease‐modifying therapies are on the horizon. In this review, we assess the late‐stage pipeline of disease‐modifying candidates for AD and offer a novel classification of intervention candidates by treatment paradigms—groups of candidates that share an underlying biological mechanism of action and general disease target.METHODSWe extracted data from the National Library of Medicine clinical trials database regarding Phase 2 and 3 trials of disease‐modifying AD therapies. We categorized trials into eight unique treatment paradigms, which we defined by combinations of therapy (biologic, small molecule, cell and gene therapy, other) and target (amyloid, tau, other). We analyzed primary endpoints, eligibility criteria including clinical ratings of cognition, trial phase and length, and funding sources.RESULTSWe identified 123 unique disease‐modifying intervention candidates in 175 late‐stage clinical trials. Biologic and small molecule drugs comprised 30% and 54% of trials, respectively. Eligibility criteria favored patients between the ages of 60 and 80 years with mild cognitive impairment. Including multi‐phase trials, 81% of studies were engaged in Phase 2 and 27% in Phase 3. Notably, within the Biologic–Amyloid paradigm, 64% of trials were engaged in Phase 3.DISCUSSIONCurrent studies of disease‐modifying therapies for AD comprise a diverse set of approaches to treating the disease. However, effort is largely concentrated in a few treatment paradigms and a narrow patient population, causing varying rates of progress among treatment paradigms in the late‐stage clinical trial pipeline. Strategies may be warranted to accelerate successes in the most promising therapeutical paradigms and nurture growth within nascent areas lacking resources but not potential.Highlights An analysis of Alzheimer's disease trial treatment paradigms was conducted. From April 2021 to March 2023, 175 trials of 123 unique candidates were reviewed. Biologic and small molecule drugs comprised 30% and 54% of trials, respectively. Eligibility criteria favored ages 60 through 80 with mild cognitive impairment.

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The Role of Dietary Antioxidants and Their Potential Mechanisms in Alzheimer’s Disease Treatment

Cited by 9 publications

References 162 publications

A Combinational Therapy for Preventing and Delaying the Onset of Alzheimer’s Disease: A Focus on Probiotic and Vitamin Co-Supplementation

A Combinational Therapy for Preventing and Delaying the Onset of Alzheimer’s Disease: A Focus on Probiotic and Vitamin Co-Supplementation

Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging

Emerging Alzheimer's disease treatment paradigms: A late‐stage clinical trial review

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