Nutraceuticals: An integrative approach to starve Parkinson's disease

Abstract

The therapeutic approach of multifactorial complex diseases is always a challenge; Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder triggered by genetic and environmental factors, contributing to its etiology. Indeed, several pathogenic mechanisms lead to selective dopaminergic neuronal injury, including oxidative stress, mitochondrial dysfunction, alteration of endoplasmic reticulum-to-Golgi protein trafficking, excitotoxicity, and neuroinflammation. Current treatment approaches include mainly dopamine replacement therapy or optimizing dopaminergic transmission; however, these strategies that do not counteract the pathogenic mechanisms underlying PD symptoms and often are less effective over time. Recently, there has been growing interest in the therapeutic use of nutraceuticals, that could represent an integrative approach to the pharmacological standard therapy and specifically affect one or more pathogenic pathways. The intake of nutraceuticals or nutritional modifications are generally safe and can be combined with current common drug therapy in most cases to improve the patient's quality of life and/or mitigate PD symptoms. The current review focuses on several key nutritional compounds and dietary modifications that are effective on several pathogenic pathways involved in PD onset and progression, and further highlights the rationale behind their potential use for the prevention and treatment of PD.

Keywords: Gut-brain axis; Mitochondrial dysfunction; Neuroinflammation; Nutraceuticals; Parkinson’s disease; Protein misfolding.

Graphical abstract

Fig. 1

Nutraceuticals limit oxidative stress and impact on mitochondrial function and dynamics. Mitochondrial dysfunction characterizing PD pathogenesis can cause cellular energy dysmetabolism with several mechanisms impacting on brain functions. Nutraceuticals can re-establish mitochondrial homeostasis acting on oxidative stress (A), defective electron transport chain (B), and altered mitochondrial dynamics (C). The unbalanced oxidative status in PD depends on several mechanisms, including the formation of α-Syn aggregates (Ludtmann et al., 2018) and the reduction of neuromelanin levels (Knorle, 2018). Various nutraceutical compounds counteract mitochondrial dysfunction as one of the major pathological mechanism of PD, reducing oxidative stress and improving mitochondrial function and efficiency.

Fig. 2

Nutraceuticals as therapeutics for PD, able to limit ER stress and protein misfolding and aggregation. The formation of misfolded proteins triggers the onset of ER stress, whose progression leads to the aggregation of proteins and eventually autophagy (Green and Levine, 2014). The main target of nutraceuticals as pharmacological treatment aims at clear misfolded proteins and reduce neurodegeneration.

Fig. 3

Nutraceuticals hold neuroprotective effects by reducing neuroinflammation. During the neurodegenerative process of PD, PAMPs and DAMPs induce the expression of TLRs, including TLR2 and TLR4. The activation of these immune mediators leads to the release of pro-inflammatory cytokines, responsible for the trigger of neuroinflammation (Kaur et al., 2017). The above-illustrated nutraceuticals limit the detrimental effects of inflammatory mediators, blunting the dopaminergic neuron loss.