Managing stress linked to effectively treating Alzheimer’s disease
The number of people suffering from Alzheimer’s disease (AD) is projected to reach 100 million by 2050
The number of people suffering from Alzheimer’s disease (AD) is projected to reach 100 million by 2050, yet there remains no effective therapy. Leading researchers worldwide are examining the role of oxidative stress (OS) in triggering AD, as well as exploring potential therapeutic targets and neuroprotective drugs to manage the disease. This research is detailed in a special supplement to the Journal of Alzheimer’s Disease, published by IOS Press.
AD is the most common form of dementia, affecting areas of the brain responsible for thought, memory, and language. It is the leading cause of disability among individuals over 65 and is one of the top 10 causes of death in the United States.
AD is characterized by the abnormal deposition of amyloid beta peptides and the accumulation of neurofibrillary tangles of hyperphosphorylated tau protein within brain cells. Despite advances in diagnosing AD, its exact cause remains unidentified.
Researchers are now looking beyond the dominant hypotheses of amyloid beta deposition and tau phosphorylation to understand the disease's underlying mechanisms.
One promising area of investigation is oxidative stress (OS), an imbalance between antioxidants and oxidants. The OS hypothesis suggests that the brain remains functional as long as "free radicals" produced during biochemical reactions are neutralized by antioxidants.
Dr. Pravat K. Mandal, guest editor of the supplement, explains: “The OS hypothesis was initiated more than a quarter century ago. Recently, researchers have shown renewed interest in investigating the potential benefits of OS neutralization, leading to numerous trials examining its effects.
As long as there is a balance between pro-oxidative molecules and antioxidants, the brain remains functional and healthy. One prominent antioxidant receiving significant attention is glutathione (GSH).”
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Clinical studies indicate that significant GSH depletion in the hippocampus can trigger early onset AD before amyloid beta deposition and tau phosphorylation. This has been validated by transgenic animal model studies.
The supplement features 12 reviews and research articles highlighting OS-based AD research from several internationally renowned laboratories.
Key findings include:
A reduced risk of developing AD is associated with dietary intake of antioxidant supplements.
Supplementation with GSH, made from the amino acids glycine, cysteine, and glutamic acid, may be neuroprotective and reduce amyloid beta or tau phosphorylation.
Significant improvement of working memory in animal models with induced dementia due to Marrubium vulgare extract suggests it may impact memory preservation.
Maintaining diversity in drug development for AD research is important for enhancing information flow from randomized clinical trials.
Dr. Mandal emphasizes, “Accumulating evidence from clinical studies leads us to the converging idea that enrichment of brain GSH is the way forward through candidates with superior bioavailability and efficacy.”
One notable study in the supplement explores the neuroprotective effect of combined treatment with epigallocatechin 3-gallate (EGCG) and melatonin (MT) on familial AD. Researchers analyzed the therapeutic potential of EGCG and MT in a three-dimensional in vitro model of familial AD with a mutation in the presenilin-1 gene. The combined treatment effectively reduced pathological markers more efficiently than individual treatments.
Drs. Marlene Jimenez-Del-Rio and Carlos Velez-Pardo from the Neuroscience Research Group at the University of Antioquia report, “Treatment with a combination of EGCG and MT can be of high therapeutic value due to the high antioxidant capacity and anti-amyloidogenic effect of both compounds compared to individual treatments, and deserves further investigation.” Dr. Mandal adds, “Combined therapy of EGCG and MT holds therapeutic promise for familial AD due to inherent antioxidant capability.”
Other important topics covered in the supplement include:
Molecular aspects of aging and age-related disorders
Potential therapeutic effects of long-term administration of Tocovid, a novel vitamin E mixture
Protective effects of coenzyme Q10 and high-intensity interval training, both individually and in combination
Efficacy of docosapentaenoic acid and/or eicosapentaenoic acid supplements in patients with mild cognitive impairment
Protective functions of the thioredoxin system and nicotinamide adenine dinucleotide phosphate in AD-induced damage
Potential strategies to address early events in AD involving microvascular deterioration in the hippocampus that precedes amyloid beta deposition
Antioxidative and anti-neuroinflammatory effects of Centella asiatica and its triterpene fractions on lipopolysaccharide-induced microglial cells for AD management
A computational system pharmacology workflow to uncover the OS triggering AD and potential therapeutic targets and neuroprotective drugs
Dr. Mandal concludes, “I anticipate that the OS hypothesis will gain its rightful recognition sooner in AD research, guiding drug development that will effectively reduce OS and preserve cognitive function.”
Dr. George Perry, Editor-in-Chief of the Journal of Alzheimer’s Disease, adds, “The discovery of OS as upstream to amyloid beta and tau deposition places it at the crossroads of effective therapeutic intervention. Dr. Mandal’s issue explores the state of the science and inspires further development.”
By focusing on OS and its role in AD, researchers are opening new avenues for therapeutic interventions that could potentially slow or prevent the progression of this devastating disease. As the understanding of AD continues to evolve, these insights offer hope for more effective treatments in the future.
For more science news stories check out our New Discoveries section at The Brighter Side of News.
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