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Chemical Epigenetics
This book presents an authoritative review of the most significant findings about all the epigenetic targets (writers, readers, and erasers) and their implication in physiology and pathology. The book also covers the design, synthesis and biological validation of epigenetic chemical modulators, which can be useful as novel chemotherapeutic agents. Particular attention is given to the chemical mechanisms of action of these molecules and to the drug discovery prose which allows their identification. This book will appeal to students who want to know the extensive progresses made by epigenetics (targets and modulators) in the last years from the beginning, and to specialized scientists who need an instrument to quickly search and check historical and/or updated notices about epigenetics.
The DNA, RNA, and Histone Methylomes
This book reviews the chemical, regulatory, and physiological mechanisms of protein arginine and lysine methyltransferases, as well as nucleic acid methylations and methylating enzymes. Protein and nucleic acid methylation play key and diverse roles in cellular signalling and regulating macromolecular cell functions. Protein arginine and lysine methyltransferases are the predominant enzymes that catalyse S-adenosylmethionine (SAM)-dependent methylation of protein substrates. These enzymes catalyse a nucleophilic substitution of a methyl group to an arginine or lysine side chain nitrogen (N) atom. Cells also have additional protein methyltransferases, which target other amino acids in peptidy...
Learning and Memory
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Preclinical and clinical issues in Alzheimer’s disease drug research and development
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive dysfunction and memory loss, inability to perform the activities of daily living and mood disorders. According to the so-called “amyloid cascade hypothesis”, amyloid-ß- peptide (Aß), produced by beta- and gamma- secretase-mediated cleavages of the amyloid precursor protein (APP), plays a pivotal role in the pathogenesis of AD. Aß was also shown to contribute to AD pathology by stimulating the hyperphosphorylation of tau which is responsible for the formation of neurofibrillary tangles. However, the “amyloid cascade hypothesis” was challenged by other theories which lend suppor...
Immunologic tumor microenvironment modulators for turning ”cold“ tumors to ”hot“ tumors
Cancer immunotherapy is based on using the immune system components to fight tumors, without destroying normal cells. Several immunotherapeutic strategies have been investigated and proposed for the treatment of cancers, including cancer vaccines containing tumor antigens that are used to induce immune responses against tumors, monoclonal antibodies against tumor antigens, and immune checkpoint inhibitors. However, many clinical trials have shown that the use of these methods as monotherapy is ineffective in many cases. Many tumors can resist immunotherapy due to the absence or insufficient infiltration of tumors with CD8+ T cells and hence, are called “cold” or non-inflammatory tumors. ...
Epigenetic Drug Discovery
This broad view of epigenetic approaches in drug discovery combines methods and strategies with individual targets, including new and largely unexplored ones such as sirtuins and methyl-lysine reader proteins. Presented in three parts - Introduction to Epigenetics, General Aspects and Methodologies, and Epigenetic Target Classes - it covers everything any drug researcher would need in order to know about targeting epigenetic mechanisms of disease. Epigenetic Drug Discovery is an important resource for medicinal chemists, pharmaceutical researchers, biochemists, molecular biologists, and molecular geneticists.
Autophagy in Tissue Injury and Homeostasis
Autophagy (“auto-digestion”), a lysosome-dependent process, degrades and turns over damaged or senescent organelles and proteins. Autophagy is a highly regulated process that impacts several vital cellular responses, including inflammation, cell death, energy metabolism, and homeostasis of organelles (mitochondria and others). Although the role of autophagy in the maintenance of tissue homeostasis is well documented, its role during tissue injury and regeneration is still emerging. In this Special Issue on “Autophagy in Tissue Injury and Homeostasis”, we focus on the roles of autophagy in systemic, specific tissue (organs/cells) injury or organ failure associated with sepsis, inflammation, metabolic disorder, toxic chemicals, ischemia-reperfusion injury, hypoxic oxidative stress, tissue fibrosis, trauma, and nutrient starvation. The knowledge gained from the identification and characterization of new molecular mechanisms will shed light on biomedical applications for tissue protection through the modulation of autophagy.
Sirtuins in Biology and Disease
Sirtuins comprise a family of NAD+-dependent enzymes that have been shown to impact longevity in a number of eukaryotic organisms. Sir2 (Silent Information Regulator 2) was the first sirtuin protein discovered. The discovery that Sir2 requires NAD+ for its activity suggested a link between Sir2 activity and the phenomenon of caloric restriction in prolonging longevity. This link was strengthened by the observation that lifespan extension by caloric restriction requires Sir2 protein. Under conditions of caloric restriction, NAD+ levels are high, Sir2 is activated, and the rate of aging is decreased. These effects have been replicated in invertebrate organisms, where a close structural and fun...
AACR 2022 Proceedings: Part B April 11-13
The AACR Annual Meeting is the focal point of the cancer research community, where scientists, clinicians, other health care professionals, survivors, patients, and advocates gather to share the latest advances in cancer science and medicine. From population science and prevention; to cancer biology, translational, and clinical studies; to survivorship and advocacy; the AACR Annual Meeting highlights the work of the best minds in cancer research from institutions all over the world.
