Alzheimer's disease and Protein Oxidation in Aging Mental

Biraben Quartarone^*
*Correspondence: Biraben Quartarone, Department of Neuroscience, University of Calgary, Calgary, AB T2N 1N4, Canada, Email:

Introduction

Alzheimer's disease, a progressive neurodegenerative disorder, continues to pose significant challenges to both patients and researchers worldwide. While its exact etiology remains elusive, scientists have been exploring various factors contributing to its development and progression. Among these, protein oxidation has emerged as a crucial aspect in understanding the pathogenesis of Alzheimer's disease, particularly concerning aging mental health. Alzheimer's disease is characterized by the accumulation of abnormal protein deposits in the brain, leading to the impairment of cognitive function and memory loss. These deposits primarily consist of beta-amyloid plaques and tau tangles, which disrupt neuronal communication and ultimately result in cell death [1].

Aging is the single most significant risk factor for Alzheimer's disease, with the prevalence of the condition increasing exponentially after the age of 65. Aging is accompanied by a gradual decline in cellular function, including impaired protein homeostasis. Protein oxidation, a hallmark of aging, occurs when Reactive Oxygen Species (ROS) interact with proteins, causing damage to their structure and function. OS are natural byproducts of cellular metabolism, but their levels can escalate due to various factors such as environmental stressors, inflammation, and mitochondrial dysfunction. When ROS production surpasses the body's antioxidant defenses, oxidative stress ensues, leading to widespread damage to biomolecules, including proteins. Oxidative stress promotes the aggregation of betaamyloid peptides into neurotoxic oligomers and fibrils. These aggregated forms of beta-amyloid are more resistant to degradation and clearance, exacerbating their accumulation in the brain [2].

Description

Oxidative stress also contributes to the hyperphosphorylation of tau protein, a process critical for the formation of neurofibrillary tangles. Hyperphosphorylated tau loses its ability to stabilize microtubules, leading to cytoskeletal instability and neuronal dysfunction. Oxidative damage to proteins compromises neuronal integrity and function, triggering neuroinflammatory responses. Activated microglia and astrocytes release pro-inflammatory cytokines and reactive oxygen species, further exacerbating oxidative stress and neuronal damage. Oxidative modification of proteins can impair the ubiquitin-proteasome system and autophagy, two essential pathways for protein clearance. This leads to the accumulation of damaged proteins, including beta-amyloid and hyperphosphorylated tau, exacerbating neurodegeneration. Understanding the role of protein oxidation in Alzheimer's disease opens avenues for therapeutic interventions aimed at mitigating oxidative stress and preserving protein homeostasis. Antioxidants such as vitamins C and E, flavonoids, and polyphenols can scavenge ROS and reduce oxidative damage to proteins. However, clinical trials investigating the efficacy of antioxidant supplements in Alzheimer's disease have yielded mixed results, highlighting the need for further research. Enhancing the activity of the ubiquitin-proteasome system and autophagy through pharmacological agents or lifestyle interventions (e.g., exercise, fasting) could facilitate the clearance of damaged proteins implicated in Alzheimer's disease pathology. Targeting neuroinflammation through the use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) or anti-inflammatory cytokine inhibitors may help alleviate oxidative stress and mitigate neuronal damage in Alzheimer's disease [3].

Protein oxidation represents a crucial link between aging and Alzheimer's disease, contributing to the pathological processes underlying neurodegeneration. Targeting oxidative stress and restoring protein homeostasis hold promise as therapeutic strategies for delaying disease onset and progression. However, further research is needed to elucidate the intricate mechanisms involved and translate these findings into effective clinical interventions. Lifestyle factors such as diet, exercise, and sleep play significant roles in modulating oxidative stress and protein homeostasis. Adopting a Mediterranean diet rich in antioxidants and omega-3 fatty acids has been associated with a reduced risk of Alzheimer's disease. Regular physical activity promotes antioxidant defenses and enhances protein clearance pathways, while sufficient sleep facilitates cellular repair and detoxification processes [3].

Emerging evidence suggests that nutritional interventions targeting protein quality control mechanisms may offer neuroprotective effects in Alzheimer's disease. Caloric restriction and dietary supplementation with specific amino acids (e.g., methionine restriction, supplementation with glycine or cysteine) have been shown to improve protein folding, reduce oxidative stress, and enhance cognitive function in preclinical models. Mitochondrial dysfunction is a key driver of oxidative stress in Alzheimer's disease, as mitochondria are major producers and targets of reactive oxygen species. Therapeutic strategies aimed at preserving mitochondrial function, such as mitochondrial antioxidants, mitochondrial biogenesis inducers, and mitophagy enhancers, hold promise for mitigating oxidative damage and alleviating neurodegeneration. Given the heterogeneity of Alzheimer's disease pathology and the multifactorial nature of protein oxidation, personalized medicine approaches may be necessary for optimal therapeutic outcomes. Biomarker-based diagnostics and stratification of patients based on their molecular profiles could facilitate the identification of individuals most likely to benefit from specific interventions targeting protein oxidation and aging-related pathways [4].

Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA regulation, play essential roles in regulating gene expression patterns associated with aging and Alzheimer's disease. Oxidative stress can induce epigenetic alterations that contribute to neurodegeneration by dysregulating synaptic plasticity, neuroinflammation, and protein homeostasis. Targeting epigenetic modifiers with small molecule inhibitors or epigenomeediting technologies holds promise for restoring aberrant gene expression patterns and ameliorating Alzheimer's disease pathology. The development of reliable blood-based biomarkers for Alzheimer's disease is a critical unmet need in the field, enabling early diagnosis, monitoring disease progression, and evaluating therapeutic efficacy. Oxidative stress-related biomarkers, such as lipid peroxidation products, protein carbonyls, and antioxidant enzyme activity, show promise for reflecting disease severity and predicting cognitive decline in Alzheimer's disease patients. Incorporating these biomarkers into clinical trials could facilitate patient stratification and enable more precise assessment of treatment responses [5].

Conclusion

Impaired cerebral blood flow regulation and blood-brain barrier dysfunction are common features of Alzheimer's disease, exacerbating oxidative stress and neuroinflammation in the brain. Endothelial dysfunction, reduced nitric oxide bioavailability, and microvascular rarefaction compromise nutrient delivery, waste clearance, and antioxidant defense mechanisms, exacerbating neuronal damage and cognitive decline. Therapeutic strategies targeting neurovascular coupling, endothelial function, and blood-brain barrier integrity may mitigate oxidative stress-induced neurodegeneration and improve cognitive outcomes in Alzheimer's disease patients. Incorporating these additional perspectives underscores the multifaceted nature of Alzheimer's disease pathogenesis and the complex interplay between oxidative stress, aging, and environmental factors. By addressing these interconnected mechanisms comprehensively, researchers aim to develop more effective preventive and therapeutic strategies for Alzheimer's disease, ultimately improving patient outcomes and quality of life.

Acknowledgement

None.

Conflict of Interest

None.

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