Abstract
Neurodegenerative disorders constitute a group of multifaceted conditions characterized by the progressive loss of neurons and synaptic connections consequent to a combination of specific genetic predispositions and stochastic stressors. The neuropathologies observed in both Alzheimer’s and Parkinson’s disease are in part attributed to compounding intrinsic and extrinsic environmental stressors, which we propose may be limited by the administration of specific grape derived phytochemicals and their metabolized derivatives, specifically polyphenols isolated from grape botanicals. Current therapies for neurodegenerative disorders are limited as they solely target the final disease pathologies including behavioral changes, cognitive deficits, proteinopathies and neuronal loss; however, this strategy is not a sustainable approach toward managing disease onset or progression. This review discusses the application of grape derived polyphenols as an adjunctive treatment paradigm for the prevention of neuropathologies associated with Alzheimer’s disease, Parkinson’s disease and Chronic Traumatic Encephalopathy by simultaneously ameliorating two stochastic stressors that facilitate their disease pathologies: inflammation and oxidative stress. The biophysical attributes of grape-derived polyphenols buffer against redox potential dependent peripheral and neuroinflammation and down regulate the activation of inflammasomes in microglia and astrocytes, which could provide a novel mechanism through which grape-derived polyphenols simultaneously suppress risk factors across pathologically distinct neurodegenerative conditions. This approach therefore offers a prophylactic mode, not feasible through current pharmacological agents, to target activity dependent risk factors for neurodegenerative disorders that manifest over an individual’s lifetime.
Highlights
Neurodegeneration is the defining feature of a group of age-related neurological disorders characterized by the progressive atrophy of neurons in cortical and subcortical brain structures
Identifying toxins and stressors responsible for altering homeostatic processes has been an imperative of research efforts, and has measurably strengthened our understanding of how neurodegeneration develops in certain environmental settings
This study found no differences in the activity of α, β- or γ-secretases or insulin-degrading enzyme (IDE) indicating that the clearance of Aβ was not affected and the mechanism of Grape Seed Polyphenol Extract (GSPE) may be a result of preventing Aβ’s initial aggregation
Summary
Neurodegeneration is the defining feature of a group of age-related neurological disorders characterized by the progressive atrophy of neurons in cortical and subcortical brain structures. Elevated markers of inflammation and oxidative stress are pervasive in all brain regions in AD and serves as important biomarkers and potential pathological targets, as they promote Aβ deposition, microglia activation, and BBB permeability
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