Nootropic foods in neurodegenerative diseases: mechanisms, challenges, and future

Abstract

Neurodegenerative diseases (NDDs) such as Alzheimer's and Parkinson's disease are increasing globally and represent a significant cause of age-related death in the population. Recent studies emphasize the strong association between environmental stressors, particularly dietary factors, and brain health and neurodegeneration unsatisfactory outcomes. Despite ongoing efforts, the efficiency of current treatments for NDDs remains wanting. Considering this, nootropic foods with neuroprotective effects are of high interest as part of a possible long-term therapeutic strategy to improve brain health and alleviate NDDs. However, since it is a new and emerging area in food and neuroscience, there is limited information on mechanisms and challenges to consider for this to be a successful intervention. Here, we seek to address these gaps by presenting a comprehensive review of possible pathways or mechanisms including mutual interactions governing nootropic food metabolism, linkages of the pathways with NDDs, intake, and neuroprotective properties of nootropic foods. We also discuss in-depth intervention with nootropic compounds and dietary patterns in NDDs, providing a detailed exploration of their mechanisms of action. Additionally, we analyze the demand, challenges, and future directions for successful development of nootropic foods targeting NDDs.

Keywords: Diets; Environmental stressors; Neurodegenerative diseases; Neuroprotective foods; Nootropic foods.

Fig. 1

Effects of environmental stressors and nootropic foods on pathways leading to neurodegenerative diseases. HPA: hypothalamic–pituitary–adrenal axis; SNS: sympathetic nervous system; ROS: reactive oxygen species; BBB: blood–brain barrier; SCFAs: short-chain fatty acids

Fig. 2

Major pathways of neurodegenerative diseases that are closely related to environmental stressors and food metabolites. The five major pathways of NDDs include: (1) excitotoxicity; (2) neuro-inflammation; (3) formation of misfolded protein plaques; (4) mitochondrial dysfunction; and (5) oxidative stress. Functional components such as polyphenols and short-chain fatty acids (SCFAs) can reverse or prevent these pathways. NMDAR: N-methyl D-aspartate receptor; TLR-4: toll-like receptor 4; TNFR1: tumor necrosis factor receptor 1; GPCRs: G-protein-coupled receptors; IKK: IkappaB kinase; NF-κB: nuclear factor kappa B; TNF-α: tumor necrosis factor-alpha; IL: interleukin; PGE₂: prostaglandin E2; NO: nitric oxide; iNOS: inducible nitric oxide synthase; COX-2: cyclooxygenase 2; NOX-2: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2; GSK-3β: glycogen synthase kinase 3 beta; CREB: cAMP (cyclic adenosine 3′,5′-monophosphate) response element-binding protein; SIRT1: sirtuin 1; PI3K: phosphoinositide-3-kinase; Akt: protein kinase B; JNK: c-Jun-N terminal kinase; p38-MAPK: p38 mitogen-activated protein kinase; p53: transcription factor p53; ERK1/2: extracellular signal-regulated kinase ½; Bcl2: protein B cell lymphoma 2; AIF: apoptosis-inducing factor; CytC: cytochrome c; GPx: glutathione peroxidase; GSH: glutathione; Nrf2: nuclear factor erythroid-2-related factor 2; γ-GCL: gamma-glutamyl cysteine ligase; SOD1: superoxide dismutase 1

Fig. 3

Some specific biomarkers for neurodegenerative diseases. Aβ: Amyloid beta; TDP-43: TAR-DNA-binding protein 43; Iba1: ionized calcium-binding adaptor molecule 1; GFAP: glial fibrillary acidic protein; PSD-95: postsynaptic density protein 95; NfL: neurofilament light chain; OCBs: oligoclonal bands; MBP: myelin basic protein

Fig. 4

The major digestive process and absorption of polyphenol-rich ingredients