Oxidative stress, the blood-brain barrier and neurodegenerative diseases: The critical beneficial role of dietary antioxidants

Abstract

In recent years, growing awareness of the role of oxidative stress in brain health has prompted antioxidants, especially dietary antioxidants, to receive growing attention as possible treatments strategies for patients with neurodegenerative diseases (NDs). The most widely studied dietary antioxidants include active substances such as vitamins, carotenoids, flavonoids and polyphenols. Dietary antioxidants are found in usually consumed foods such as fresh fruits, vegetables, nuts and oils and are gaining popularity due to recently growing awareness of their potential for preventive and protective agents against NDs, as well as their abundant natural sources, generally non-toxic nature, and ease of long-term consumption. This review article examines the role of oxidative stress in the development of NDs, explores the 'two-sidedness' of the blood-brain barrier (BBB) as a protective barrier to the nervous system and an impeding barrier to the use of antioxidants as drug medicinal products and/or dietary antioxidants supplements for prevention and therapy and reviews the BBB permeability of common dietary antioxidant suplements and their potential efficacy in the prevention and treatment of NDs. Finally, current challenges and future directions for the prevention and treatment of NDs using dietary antioxidants are discussed, and useful information on the prevention and treatment of NDs is provided.

Keywords: Blood–brain barrier; Carotenoids; Dietary antioxidant supplements; Flavonoids; Neurodegenerative diseases; Oxidative stress; Polyphenols; Vitamins.

Graphical abstract

Figure 1

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases (NDs). The pathology of NDs [including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS)] is closely related to the production of oxidative stress, which in turn promotes the further development of NDs. Excessive production of active substances will lead to oxidative damage of proteins, lipids and nucleic acids and induce the formation of misfolded amyloid-β (Aβ), α-synuclein (α-syn), mutant Huntington protein and superoxide dismutase 1, resulting in neurodegeneration.

Figure 2

The structure and permeability of the blood–brain barrier (BBB). (a) Permeability of the BBB. The BBB separates the brain from the components of circulating blood and is formed by endothelial cells connected by tight junction proteins (TJs). TJs allow essential nutrients (such as oxygen, glucose, amino acids, among others) to enter the brain parenchyma through simple diffusion, passive diffusion between cells (paracellular) or through cells (transcellular) and via transporters that transport essential macromolecules. It limits the entry of potentially harmful molecules in the blood (about 98% of drugs) into the brain. (b) Structure of the neurovascular unit of the BBB. The capillary cavity is surrounded by endothelial cells, and the TJs are located between brain endothelial cells, preventing most substances from flowing into the brain from the blood. Endothelial cells and pericytes are surrounded by a common basement membrane. The ends of astrocytes surround endothelial cells and pericytes and provide connections between neurons and BBB. (c) The basic molecular structure of TJ protein complexes of BBB. Claudins and occludin compress two adjacent endothelial cells together. These proteins are linked to cytoskeletal proteins (actin) through helper proteins such as ZOs (zona occludens), which promote the formation of TJs.

Figure 3

Antioxidant effects of dietary antioxidants in the prevention and treatment of neurodegenerative diseases (NDs). Dietary antioxidants reduce oxidative stress by inhibiting lipid peroxidation, scavenging reactive oxygen species (ROS), and increasing the activity of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px)] and the level of antioxidant molecule glutathione (GSH). They significantly increase the expression of nuclear factor erythroid 2 like 2 (NRF2), inhibit the expression of nuclear transcription factor kappa B (NF-κB), and directly reduce the excessive production of ROS. By effectively reducing amyloid-β (Aβ) deposition and TAU protein phosphorylation, they can improve neurodegeneration.

Figure 4

Main types and food sources of dietary antioxidants. The most widely studied dietary antioxidants include vitamins, carotenoids, flavonoids, non-flavonoid polyphenols, phenolic acids and other substances. They mainly exist in fresh fruits, vegetables, nuts and oils.