Anti-inflammatory role of gold nanoparticles in the prevention and treatment of Alzheimer’s disease

Source: Anti-inflammatory role of gold nanoparticles in the prevention and treatment of Alzheimer’s disease

1. Introduction

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, and the age-standardized prevalence of dementia in people over 60 is 5–7%. It has become a global health problem, costing up to $604 billion annually.1 In 2018, about 50 million people had dementia worldwide, and age is a major factor contributing to dementia. AD is a neurodegenerative disease that causes memory and cognitive dysfunction and reduces a person's decision-making and reasoning functions.2 People with AD are at higher risk of stroke, chronic obstructive pulmonary disease, and suicide than the general population, placing a heavy burden on patients and society. AD is a multifactorial disease, and the pathogenesis and pathophysiological mechanisms have not been fully elucidated.3 Multiple factors combine to cause AD, with amyloid β-protein (Aβ) deposition, the formation, and proliferation of neurogenic fiber tangles composed of the microtubule-associated protein taurine (Tau), dysregulation of protein degradation pathways, loss of support from neurotrophic factors, and synaptic and neuronal loss being the main pathological features of AD.4

Currently, the primary treatment for AD is medication. Cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists can be used to treat AD.5 However, drug therapy can only temporarily relieve symptoms and cannot change the natural history of AD patients.6 As AD patients enter advanced stages, neurodegeneration increases, and they cannot repair damaged neural networks by reducing amyloid, so new drug strategies are urgently needed.7 Recent studies have shown that the inflammatory response is closely related to the onset and progression of AD and that suppressing or eliminating inflammation may help to treat AD.8 Firstly, patients with AD have activated microglia around amyloid plaques, activated T cells in the brain parenchyma, and increased expression of pro-inflammatory cytokines in the peripheral and central nervous systems (CNS). There is an accumulation of Aβ in the nervous system of AD patients. Furthermore, the deposition of Aβ leads to the release of pro-inflammatory cytokines such as interleukin-1α (IL-1α), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), gamma-interferon (IFN-g), reactive oxygen species (ROS), and nitric oxide (NO).9 These factors activate microglia and the complement system, which exacerbate the inflammatory response and induce the expression of amyloid precursor protein (APP).10 The increase of APP will, in turn, upregulate the expression of Aβ, forming a vicious circle, leading to neuronal dysfunction or even death and aggravating AD.11 Generally, inflammation subsides independently, however, persistent inflammatory responses can become chronic inflammation and impair brain function.12 Moreover, long-term use of anti-inflammatory drugs reduces the incidence of AD to some extent.13 This confirms that neuroinflammation may be closely related to the development of AD, so anti-inflammatory medications may be an effective way to treat AD.

Nanomaterials have an important role in disease treatment and diagnosis, novel drug synthesis, and drug delivery, and they have been widely used in biomedical, engineering, and health research fields.14 Among them, nanomedicine is an important branch of nanomaterials that can help medical practitioners to improve the accuracy of diagnosis and have good efficacy.15 Nanomedicine is used in the treatment of cancer, rapid detection of AIDS, and on-demand exogenous insulin release for diabetes, Anti-inflammation, etc.16 Recent studies have shown that nanoparticles have advantages over traditional materials in anti-inflammatory and treating central nervous system diseases.17 AuNPs are an emerging type of nanoparticles. On the one hand, it can penetrate the blood–brain barrier (BBB) and reach the central nervous system to exert therapeutic effects. On the other hand, AuNPs of 40–50 nm in the concentration range of 10 mg kg−1 can effectively reduce the inflammatory response in rats.18 Therefore, given their excellent anti-inflammatory effect, AuNPs may be a promising option for treating Alzheimer's.

Multiple studies have shown that AuNPs reduce the inflammatory response and facilitate tissue repair. AuNPs induce polarization of microglia toward the M2 phenotype, thereby reducing pro-inflammatory cytokines expressed by microglia in the M1 phenotype and increasing anti-inflammatory cytokines expressed by the M2 phenotype, reducing neuroinflammation.19 In addition, AuNPs inhibit the activation of MAPK, NF-κB, JAK/STAT, and IKK-α/β signaling pathways, suppressing their downstream factors.20 AuNPs reduce the expression of ICAM-1 in circulating polymorphonuclear (PMN) leukocytes and endothelial cells and inhibit leukocyte adhesion.21 AuNPs scavenge ROS from mitochondria, inhibit the production of reactive oxygen and nitrogen species, and suppress oxidative stress.22 Injecting 20 nm of AuNPs into the peritoneal cavity of AD model rats, AuNPs were found to reduce Tau phosphorylation caused by okadaic acid significantly. It also increased IL-4 expression levels in the rat cortex and hippocampus, reduced inflammation, and mitochondrial oxidative stress, and prevented cognitive impairment in rats.22 In summary, AuNPs effectively reduce the inflammatory response and may help control AD development.

2. Overview of AuNPs

Nanotechnology is proliferating in the 21st century with its wide range of applications and great potential.23By observing, manipulating, assembling, and controlling matter from the nanoscale, nanotechnology has prepared new nanomaterials for use in various fields, including chemistry, biology, engineering, and medicine.24Nanomaterials are classified into inorganic (e.g., metals) and organic nanomaterials (e.g., proteins, lipids) and possess rich structural properties.25In the biomedical field, nanomaterials show great promise in targeted drug delivery, diagnostic testing, evaluation, and treatment of diseases by engaging in biomolecular interactions through manipulable physical, chemical, and biological properties.26

AuNPs, as a kind of noble metal nanostructures, show high activity differentiated from the macroscopic size. The properties of AuNPs are closely related to their shape and size. Currently, many different shapes of AuNPs have been developed, including rod, sphere, cage, shell, etc. (Fig. 1).27 The shapes of AuNPs can confer unique advantages, such as rod-shaped AuNPs with good photothermal properties, while cage-shaped AuNPs are more suitable for loading drugs.28 In addition, the electrical conductivity of AuNPs is affected by the particle size. Au nanocrystals (particle size >2 nm) have conductive properties, while au nanoclusters (particle size <2 nm) have insulating properties.29

References can be found in the full paper.

READ FULL PAPER HERE...