Alzheimer’s disease (AD) is the leading cause of dementia worldwide. Most AD patients develop the disease in late life, named late onset AD (LOAD). Currently, the most recognized explanation for AD pathology is the amyloid cascade hypothesis. It is assumed that amyloid beta (Aβ) aggregation and deposition are critical pathogenic processes in AD, leading to the formation of amyloid plaques, as well as neurofibrillary tangles, neuronal cell death, synaptic degeneration, and dementia. In LOAD, the causes of Aβ accumulation and neuronal loss are not completely clear. Importantly, the blood–brain barrier (BBB) disruption seems to present an essential role in the induction of neuroinflammation and consequent AD development. In addition, we propose that the systemic inflammation triggered by conditions like metabolic diseases or infections are causative factors of BBB disruption, coexistent inflammatory cascade and, ultimately, the neurodegeneration observed in AD. In this regard, the use of anti-inflammatory molecules could be an interesting strategy to treat, delay or even halt AD onset and progression. Herein, we review the inflammatory cascade and underlying mechanisms involved in AD pathogenesis and revise the anti-inflammatory effects of compounds as emerging therapeutic drugs against AD.

Duchenne muscular dystrophy (DMD) is an X-linked recessive hereditary myopathy characterized by progressive muscle degeneration in male children. As a consequence of DMD, increased inflammation and oxidative stress occur in muscle tissue along with morphological changes. Several studies have reported anti-inflammatory and antioxidant effects of gold nanoparticles (GNP) in muscle injury models. The objective of this study was to evaluate these effects along with the impacts of the disease on histopathological changes following chronic administration of GNP to Mdx mice. Two-month-old Mdx mice were separated into five groups of eight individuals each, as follows: wild-type (WT), Mdx-modified without treatment, Mdx +2.5 mg/kg GNP, Mdx +7.0 mg/kg GNP, and Mdx +21 mg/kg GNP. GNP with a mean diameter of 20 nm were injected subcutaneously at concentrations of 2.5, 7.0, and 21 mg/kg. Treatments continued for 30 days with injections administered at 48-hour intervals. Twenty-four hours after the last injection, the animals were killed, and the central region of the gastrocnemius muscle was surgically removed. Chronic administration of GNP reduced inflammation in the gastrocnemius muscle of Mdx mice and reduced morphological alterations due to inflammatory responses to muscular dystrophy. In addition, GNP also demonstrated antioxidant potential by reducing the production of reactive oxygen and nitrogen species, reducing oxidative damage, and improving antioxidant activity.

Insulin resistance is the link between obesity and type 2 diabetes mellitus. The molecular mechanism by which obese individuals develop insulin resistance has not yet been fully elucidated; however, inconclusive and contradictory studies have shown that oxidative stress may be involved in the process. Thus, this study aimed to evaluate the effect of reactive species on the mechanism of insulin resistance in diet-induced obese mice. Obese insulin-resistant mice were treated with N-acetylcysteine (NAC; 50 mg/kg per day, for 15 days) by means of oral gavage. Twenty-four hours after the last NAC administration, the animals were euthanized and their tissues were extracted for biochemical and molecular analyses. NAC supplementation induced improved insulin resistance and fasting glycemia, without modifications in food intake, body weight, and adiposity. Obese mice showed increased dichlorofluorescein (DCF) oxidation, reduced catalase (CAT) activity, and reduced glutathione levels (GSH). However, treatment with NAC increased GSH and CAT activity and reduced DCF oxidation. The gastrocnemius muscle of obese mice showed an increase in nuclear factor kappa B (NFκB) and protein tyrosine phosphatase (PTP1B) levels, as well as c-Jun N-terminal kinase (JNK) phosphorylation compared to the control group; however, NAC treatment reversed these changes. Considering the molecules involved in insulin signaling, there was a reduction in insulin receptor substrate (IRS) and protein kinase B (Akt) phosphorylation. However, NAC administration increased IRS and Akt phosphorylation and IRS/PI3k (phosphoinositide 3-kinase) association. The results demonstrated that oxidative stress-associated obesity could be a mechanism involved in insulin resistance, at least in this animal model.