Pleiotropic Protective Effects of Phytochemicals in Alzheimer's Disease

Alzheimer's disease (AD) is a severe chronic neurodegenerative disorder of the brain characterised by progressive impairment in memory and cognition. In the past years an intense research has aimed at dissecting the molecular events of AD. However, there is not an exhaustive knowledge about AD pathogenesis and a limited number of therapeutic options are available to treat this neurodegenerative disease. Consequently, considering the heterogeneity of AD, therapeutic agents acting on multiple levels of the pathology are needed. Recent findings suggest that phytochemicals compounds with neuroprotective features may be an important resources in the discovery of drug candidates against AD. In this paper we will describe some polyphenols and we will discuss their potential role as neuroprotective agents. Specifically, curcumin, catechins, and resveratrol beyond their antioxidant activity are also involved in antiamyloidogenic and anti-inflammatory mechanisms. We will focus on specific molecular targets of these selected phytochemical compounds highlighting the correlations between their neuroprotective functions and their potential therapeutic value in AD

Identification of Premature Senescence Cells in the Brain of the HIV-1 Transgenic Rat (HIV-TG Rat)

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The "Alzheimer's disease signature": potential perspectives for novel biomarkers

Alzheimer's disease is a progressive and neurodegenerative disorder which involves multiple molecular mechanisms. Intense research during the last years has accumulated a large body of data and the search for sensitive and specific biomarkers has undergone a rapid evolution. However, the diagnosis remains problematic and the current tests do not accurately detect the process leading to neurodegeneration. Biomarkers discovery and validation are considered the key aspects to support clinical diagnosis and provide discriminatory power between different stages of the disorder. A considerable challenge is to integrate different types of data from new potent approach to reach a common interpretation and replicate the findings across studies and populations. Furthermore, long-term clinical follow-up and combined analysis of several biomarkers are among the most promising perspectives to diagnose and manage the disease. The present review will focus on the recent published data providing an updated overview of the main achievements in the genetic and biochemical research of the Alzheimer's disease. We also discuss the latest and most significant results that will help to define a specific disease signature whose validity might be clinically relevant for future AD diagnosis

Mycoplasmas–Host Interaction: Mechanisms of Inflammation and Association with Cellular Transformation

Mycoplasmas are the smallest and simplest self-replicating prokaryotes. Located everywhere in nature, they are widespread as parasites of humans, mammals, reptiles, fish, arthropods, and plants. They usually exhibiting organ and tissue specificity. Mycoplasmas belong to the class named Mollicutes (mollis = soft and cutis = skin, in Latin), and their small size and absence of a cell wall contribute to distinguish them from other bacteria. Mycoplasma species are found both outside the cells as membrane surface parasites and inside the cells, where they become intracellular residents as “silent parasites”. In humans, some Mycoplasma species are found as commensal inhabitants, while others have a significant impact on the cellular metabolism and physiology. Mollicutes lack typical bacterial PAMPs (e.g., lipoteichoic acid, flagellin, and some lipopolysaccharides) and consequently the exact molecular mechanisms of Mycoplasmas’ recognition by the cells of the immune system is the subjects of several researches for its pathogenic implications. It is well known that several strains of Mycoplasma suppress the transcriptional activity of p53, resulting in reduced apoptosis of damaged cells. In addition, some Mycoplasmas were reported to have oncogenic potential since they demonstrated not just accumulation of abnormalities but also phenotypic changes of the cells. Aim of this review is to provide an update of the current literature that implicates Mycoplasmas in triggering inflammation and altering critical cellular pathways, thus providing a better insight into potential mechanisms of cellular transformation

Immunomodulatory and Antiaging Mechanisms of Resveratrol, Rapamycin, and Metformin: Focus on mTOR and AMPK Signaling Networks

Aging results from the progressive dysregulation of several molecular pathways and mTOR and AMPK signaling have been suggested to play a role in the complex changes in key biological networks involved in cellular senescence. Moreover, multiple factors, including poor nutritional balance, drive immunosenescence progression, one of the meaningful aspects of aging. Unsurprisingly, nutraceutical and pharmacological interventions could help maintain an optimal biological response by providing essential bioactive micronutrients required for the development, maintenance, and the expression of the immune response at all stages of life. In this regard, many studies have provided evidence of potential antiaging properties of resveratrol, as well as rapamycin and metformin. Indeed, in vitro and in vivo models have demonstrated for these molecules a number of positive effects associated with healthy aging. The current review focuses on the mechanisms of action of these three important compounds and their suggested use for the clinical treatment of immunosenescence and aging