Alzheimer’s disease (AD) is a detrimental brain disorder characterized by a gradual cognitive decline and neuronal deterioration. To date, the treatments available are effective only in the early ...stage of the disease. The AD etiology has not been completely revealed, and investigating new pathological mechanisms is essential for developing effective and safe drugs. The recreational and pharmacological properties of marijuana are known for centuries, but only recently the scientific community started to investigate the potential use of cannabinoids in AD therapy—sometimes with contradictory outcomes. Since the endocannabinoid system (ECS) is highly expressed in the hippocampus and cortex, cannabis use/abuse has often been associated with memory and learning dysfunction in vulnerable individuals. However, the latest findings in AD rodent models have shown promising effects of cannabinoids in reducing amyloid plaque deposition and stimulating hippocampal neurogenesis. Beneficial effects on several dementia-related symptoms have also been reported in clinical trials after cannabinoid treatments. Accordingly, future studies should address identifying the correct therapeutic dosage and timing of treatment from the perspective of using cannabinoids in AD therapy. The present paper aims to summarize the potential and limitations of cannabinoids as therapeutics for AD, focusing on recent pre-clinical and clinical evidence.
Recently, the role of food and nutrition in preventing or delaying chronic disability in the elderly population has received great attention. Thanks to their ability to influence biochemical and ...biological processes, bioactive nutrients are considered modifiable factors capable of preserving a healthy brain status. A diet rich in vitamins and polyphenols and poor in saturated fatty acids has been recommended. In the prospective of a healthy diet, cooking methods should be also considered. In fact, cooking procedures can modify the original dietary content, contributing not only to the loss of healthy nutrients, but also to the formation of toxins, including advanced glycation end products (AGEs). These harmful compounds are adsorbed at intestinal levels and can contribute to the ageing process. The accumulation of AGEs in ageing (“AGE-ing”) is further involved in the exacerbation of neurodegenerative and many other chronic diseases. In this review, we discuss food’s dual role as both source of bioactive nutrients and reservoir for potential toxic compounds—paying particular attention to the importance of proper nutrition in preventing/delaying Alzheimer’s disease. In addition, we focus on the importance of a good education in processing food in order to benefit from the nutritional properties of an optimal diet.
The use of electrochemical sensors for the analysis of biological samples is nowadays widespread and highly demanded from diagnostic and pharmaceutical research, but the reliability and repeatability ...still remain debated issues. In the expanding field of printed electronics, Aerosol Jet Printing (AJP) appears promising to bring an improvement in resolution, miniaturization, and flexibility. In this paper, the use of AJP is proposed to design and fabricate customized electrochemical sensors in term of geometry, materials and 3D liquid sample confinement, reducing variability in the functionalization process. After an analysis of geometrical, electrical and surface features, the optimal layout has been selected. An electrochemical test has been then performed quantifying Interleukin-8, selected as reference protein, by means of Anodic Stripping Voltammetry. AJP sensors have been compared with standard screen-printed electrodes in terms of current density and relative standard deviation. Results from AJP sensors with Ag-based Anodic Stripping Voltammetry confirmed nanostructures capability to reduce the limit of detection (from 2.1 to 0.3 ng/mL). Furthermore, AJP appeared to bring an improvement in term of relative standard deviation from 50 to 10%, if compared to screen-printed sensors. This is promising to improve reliability and repeatability of measurement techniques integrable in several biotechnological applications.
In the middle of the coronavirus disease 19 (COVID-19) outbreak, the main efforts of the scientific community are rightly all focused on identifying efficient pharmacological treatments to cure the ...acute severe symptoms and developing a reliable vaccine. On the other hand, we cannot exclude that, in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) positive subjects, the virus infection could have long-term consequences, leading to chronic medical conditions such as dementia and neurodegenerative disease. Considering the age of SARS-CoV-2 infected subjects, the neuroinvasive potential might lead/contribute to the development of neurodegenerative diseases. Here, we analyzed a possible link between SARS-CoV-2 infection and Alzheimer's disease risk, hypothesizing possible mechanisms at the base of disease development. This reflection raises the need to start to experimentally investigating today the mechanistic link between Alzheimer's disease (AD) and COVID-19 to be ready tomorrow.
Redox homeostasis may be defined as the dynamic equilibrium between electrophiles and nucleophiles to maintain the optimum redox steady state. This mechanism involves complex reactions, including ...nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, activated by oxidative stress in order to restore the redox balance. The ability to maintain the optimal redox homeostasis is fundamental for preserving physiological functions and preventing phenotypic shift toward pathological conditions. Here, we reviewed mechanisms involved in redox homeostasis and how certain natural compounds regulate the nucleophilic tone. In addition, we focused on the antioxidant properties of rice and particularly on its bioactive compound, γ-oryzanol. It is well known that γ-oryzanol exerts a variety of beneficial effects mediated by its antioxidant properties. Recently, γ-oryzanol was also found as a Nrf2 inducer, resulting in nucleophilic tone regulation and making rice a para-hormetic food.
Aging, dementia, and cancer share a critical set of altered cellular functions in response to DNA damage, genotoxic stress, and other insults. Recent data suggest that the molecular machinery ...involved in maintaining neural function in neurodegenerative disease may be shared with oncogenic pathways. Cancer and neurodegenerative diseases may be influenced by common signaling pathways regulating the balance of cell survival versus death, a decision often governed by checkpoint proteins. This paper focuses on one such protein, p53, which represents one of the most extensively studied proteins because of its role in cancer prevention and which, furthermore, has been recently shown to be involved in aging and Alzheimer disease (AD). The contribution of a conformational change in p53 to aging and neurodegenerative processes has yet to be elucidated. In this review we discuss the multiple functions of p53 and how these correlate between cancer and neurodegeneration, focusing on various factors that may have a role in regulating p53 activity. The observation that aging and AD interfere with proteins controlling duplication and cell cycle may lead to the speculation that, in senescent neurons, aberrations in proteins generally dealing with cell cycle control and apoptosis could affect neuronal plasticity and functioning rather than cell duplication.
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► Multiple functions of p53 correlate between cancer and neurodegeneration. ► p53 maintains a delicate balance between cancer-suppressive and age-promoting functions. ► A conformational mutant p53 in cancer and aging is discussed. ► p53 is a transcription factor critical to decisions about cell fate.
Artemisia annua L. (AA) has shown for many centuries important therapeutic virtues associated with the presence of artemisinin (ART). The aim of this study was to identify and quantify ART and other ...secondary metabolites in ethanolic extracts of AA and evaluate the biological activity in the presence of an inflammatory stimulus. In this work, after the extraction of the aerial parts of AA with different concentrations of ethanol, ART was quantified by HPLC and HPLC-MS. In addition, anthocyanins, flavanols, flavanones, flavonols, lignans, low-molecular-weight phenolics, phenolic acids, stilbenes, and terpenes were identified and semi-quantitatively determined by UHPLC-QTOF-MS untargeted metabolomics. Finally, the viability of human neuroblastoma cells (SH-SY5Y) was evaluated in the presence of the different ethanolic extracts and in the presence of lipopolysaccharide (LPS). The results show that ART is more concentrated in AA samples extracted with 90% ethanol. Regarding the other metabolites, only the anthocyanins are more concentrated in the samples extracted with 90% ethanol. Finally, ART and all AA samples showed a protective action towards the pro-inflammatory stimulus of LPS. In particular, the anti-inflammatory effect of the leaf extract of AA with 90% ethanol was also confirmed at the molecular level since a reduction in TNF-α mRNA gene expression was observed in SH-SY5Y treated with LPS.
Understanding the earliest pathophysiological changes of Alzheimer's disease (AD) may aid in the search for timely diagnostic biomarkers and effective disease-modifying therapies. The p53 protein is ...mostly known for its role in tumor suppression. However, emerging evidence supports that dysregulated p53 activity may contribute to various peripheral and brain alterations during the earliest stages of AD. This review describes the mechanisms through which p53 dysregulation may exacerbate AD pathology and how this could be used as a potential peripheral biomarker for early detection of the disease. MAIN BODY: p53, known as the guardian of the genome, may underlie various compensation or defense mechanisms that prevent neurons from degeneration. These mechanisms include maintenance of redox homeostasis, regulation of inflammation, control of synaptic function, reduction of amyloid β peptides, and inhibition of neuronal cell cycle re-entry. Thereby, dysregulation of p53-dependent compensation mechanisms may contribute to neuronal dysfunction, thus leading to neurodegeneration. Interestingly, a conformational misfolded variant of p53, described in the literature as unfolded p53, which has lost its canonical structure and function, was observed in peripheral cells from mild cognitive impairment (MCI) and AD patients. In AD pathology, this peculiar conformational variant was caused by post-translational modifications rather than mutations as commonly observed in cancer. Although the presence of the conformational variant of p53 in the brain has yet to be formally demonstrated, the plethora of p53-dependent compensation mechanisms underscores that the guardian of the genome may not only be lost in the periphery during AD pathology.
These findings revisit the role of p53 in the early development and exacerbation of AD pathology, both in the brain and periphery. The conformational variant of p53 represents a potential peripheral biomarker that could detect AD at its earliest stages.
Rice (
L.) is the main food source for more than half of humankind. Rice is rich in phytochemicals and antioxidants with several biological activities; among these compounds, the presence of ...γ-oryzanol is noteworthy. The present study aims to explore the effects of γ-oryzanol on cognitive performance in a mouse model of neuroinflammation and cognitive alterations.
Mice received 100 mg/kg γ-oryzanol (ORY) or vehicle once daily for 21 consecutive days and were then exposed to an inflammatory stimulus elicited by lipopolysaccharide (LPS). A novel object recognition test and mRNA expression of antioxidant and neuroinflammatory markers in the hippocampus were evaluated.
ORY treatment was able to improve cognitive performance during the neuroinflammatory response. Furthermore, phase II antioxidant enzymes such as heme oxygenase-1 (HO-1) and NADPH-dehydrogenase-quinone-1 (NQO1) were upregulated in the hippocampi of ORY and ORY+LPS mice. Lastly, γ-oryzanol showed a strong anti-inflammatory action by downregulating inflammatory genes after LPS treatment.
These results suggest that chronic consumption of γ-oryzanol can revert the LPS-induced cognitive and memory impairments by promoting hippocampal antioxidant and anti-inflammatory molecular responses.
Our understanding of Alzheimer's disease (AD) pathogenesis has developed with several hypotheses over the last 40 years, including the Amyloid and Tau hypotheses. More recently, the p53 protein, ...well-known as a genome guardian, has gained attention for its potential role in the early evolution of AD. This is due to the central involvement of p53's in the control of oxidative stress and potential involvement in the Amyloid and Tau pathways. p53 is commonly regulated by post-translational modifications (PTMs), which affect its conformation, increasing its capacity to adopt multiple structural and functional states, including those that can affect brain processes, thus contributing to AD development. The following review will explore the impact of p53 PTMs on its function and consequential involvement in AD pathogenesis. The greater understanding of the role of p53 in the pathogenesis of AD could result in more targeted therapies benefiting the many patients of this debilitating disease.
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