Abstract
Neurodegenerative disorders are a widespread cause of morbidity and mortality worldwide, characterized by neuroinflammation, oxidative stress and neuronal depletion. The broad-spectrum neuroprotective activity of the Mediterranean diet is widely documented, but it is not yet known whether its nutritional and caloric balance can induce a modulation of the endocannabinoid system. In recent decades, many studies have shown how endocannabinoid tone enhancement may be a promising new therapeutic strategy to counteract the main hallmarks of neurodegeneration. From a phylogenetic point of view, the human co-evolution between the endocannabinoid system and dietary habits could play a key role in the pro-homeostatic activity of the Mediterranean lifestyle: this adaptive balance among our ancestors has been compromised by the modern Western diet, resulting in a “clinical endocannabinoid deficiency syndrome”. This review aims to evaluate the evidence accumulated in the literature on the neuroprotective, immunomodulatory and antioxidant properties of the Mediterranean diet related to the modulation of the endocannabinoid system, suggesting new prospects for research and clinical interventions against neurodegenerative diseases in light of a nutraceutical paradigm.
Highlights
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Endocannabinoids (ECs) exhibit pleiotropic activities impacting cognition, pain, appetite and inflammatory processes. They are involved in glucose and lipid metabolism, and they stimulate food uptake, so their chronic overactivation leads to the development of obesity, insulin and leptin resistance, metabolic syndrome and type 2 diabetes [2]
This review aims to reconsider some neuroprotective properties of a typical Mediterranean diet (MedD) as being linked to a rebalancing between the components of the endocannabinoid system
Summary
Analyzed for its ability to modulate pain, the endocannabinoid system is considered a powerful system, capable of regulating several physiological and pathological processes. APP/PS1 mice, expressing the mutant form of amyloid precursor protein and presenilin, treated with CB2R agonists, showed improved cognitive performance, paralleled by a lower microglial activity, suggesting that the neuroprotective role of CB2R receptors was dependent on reductions in both neurotoxicity and neuroinflammation, as well as on increased Aβ clearance, leading to improved memory and cognition [23,27] In support of this result, a follow-up study, performed in knockout CB2R mouse models of AD, showed increased levels of Aβ [28]. In a recent study on different cell lines (SH-SY5Y, C6, BV2), increased PEA levels, subsequent to downregulation of NAAA, counteracted LPS- and interferon-γ (INF-γ)-induced inflammation [47] Taking together these observations, modulation of the endocannabinoid system could be a potential wide-ranging therapeutic target in reducing the main hallmarks of neurodegeneration, including neuroinflammation, excitotoxicity and oxidative stress (OxS) [44]. This review aims to reconsider some neuroprotective properties of a typical Mediterranean diet (MedD) as being linked to a rebalancing between the components of the endocannabinoid system
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