Alzheimer's disease, specifically the basic mechanisms, structures, expression patterns, cleavage processes of amyloid plaques, and associated diagnostic and therapeutic approaches, are detailed in this chapter.
Corticotropin-releasing hormone (CRH) plays a critical role in both baseline and stress-activated processes of the hypothalamic-pituitary-adrenal (HPA) axis and extrahypothalamic brain circuits, modulating behavioral and humoral responses to stress. We delineate the cellular components and molecular mechanisms of CRH system signaling mediated by G protein-coupled receptors (GPCRs) CRHR1 and CRHR2, considering current GPCR signaling models involving both plasma membrane and intracellular compartments, thus defining the framework for spatiotemporal signal resolution. The latest studies on CRHR1 signaling in neurohormonal contexts highlight novel mechanisms underlying cAMP production and ERK1/2 activation. Within this brief overview, we also examine the pathophysiological function of the CRH system, underscoring the need for a comprehensive characterization of CRHR signaling mechanisms to develop innovative and specific treatments for stress-related disorders.
Nuclear receptors (NRs), the ligand-dependent transcription factors, govern a range of essential cellular processes such as reproduction, metabolism, and development. These NRs are categorized into seven superfamilies (subgroup 0 through subgroup 6) based on ligand-binding characteristics. biomarker panel All NRs possess a common domain structure comprising segments A/B, C, D, and E, each fulfilling unique essential functions. Hormone Response Elements (HREs), particular DNA sequences, are recognized and bonded to by NRs, appearing in the form of monomers, homodimers, or heterodimers. The efficiency of nuclear receptor binding is further modulated by minor discrepancies in the HRE sequences, the spacing between the two half-sites, and the flanking region of the response elements. Target genes of NRs can be both stimulated and inhibited by the action of NRs. In positively regulated genes, the binding of a ligand to nuclear receptors (NRs) results in the recruitment of coactivators, which subsequently initiate the activation of the target gene's expression; conversely, unliganded NRs lead to transcriptional repression. In contrast, gene silencing by NRs occurs through two separate mechanisms: (i) transcriptional repression reliant on ligands, and (ii) transcriptional repression independent of ligands. Within this chapter, the NR superfamilies will be summarized, covering their structural aspects, the molecular mechanisms behind their functions, and their impact on pathophysiological conditions. The identification of novel receptors and their corresponding ligands, along with an understanding of their functions in diverse physiological processes, may be facilitated by this approach. The development of therapeutic agonists and antagonists to control the dysregulation of nuclear receptor signaling is anticipated.
In the central nervous system (CNS), glutamate, a non-essential amino acid, is a major excitatory neurotransmitter, holding considerable influence. Ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs) are targets for this molecule, ultimately contributing to postsynaptic neuronal excitation. Their significance extends to memory function, neural growth, communication pathways, and the acquisition of knowledge. Endocytosis and the intricate subcellular trafficking of the receptor are critical factors in the regulation of receptor expression on the cell membrane and the subsequent excitation of the cells. Receptor type, ligands, agonists, and antagonists all influence the process of endocytosis and intracellular trafficking of the receptor. A comprehensive exploration of glutamate receptor types, their subtypes, and the dynamic regulation of their internalization and trafficking pathways is presented in this chapter. Briefly considering the roles of glutamate receptors in neurological diseases is also pertinent.
Neurotrophins, acting as soluble factors, emanate from neurons and the postsynaptic targets they engage with, crucial for neuronal health and development. Several processes, including neurite outgrowth, neuronal endurance, and synapse creation, are influenced by neurotrophic signaling. The internalization of the ligand-receptor complex, following the binding of neurotrophins to their receptors, tropomyosin receptor tyrosine kinase (Trk), is a key part of the signaling process. The complex is subsequently routed to the endosomal pathway, enabling the initiation of downstream signaling by Trks. Expression patterns of adaptor proteins, in conjunction with endosomal localization and co-receptor interactions, dictate the diverse mechanisms controlled by Trks. An overview of neurotrophic receptor endocytosis, trafficking, sorting, and signaling is provided in this chapter.
The principal neurotransmitter, GABA (gamma-aminobutyric acid), plays a key role in chemical synapses by suppressing neuronal activity. Within the central nervous system (CNS), it plays a crucial role in maintaining a balance between excitatory impulses (that depend on glutamate) and inhibitory impulses. Upon release into the postsynaptic nerve terminal, GABA binds to its specific receptors, GABAA and GABAB. Neurotransmission inhibition, in both fast and slow modes, is controlled by each of these two receptors. By opening chloride channels, the ligand-gated GABAA receptor decreases membrane potential, leading to the inhibition of synaptic transmission. Oppositely, GABAB receptors, classified as metabotropic, increase the concentration of potassium ions, thereby preventing the release of calcium ions and subsequently inhibiting the release of other neurotransmitters into the presynaptic membrane. Through distinct pathways and mechanisms, these receptors undergo internalization and trafficking, processes discussed in detail within the chapter. Maintaining stable psychological and neurological brain function hinges on sufficient GABA levels. Low levels of GABA have been implicated in a range of neurodegenerative diseases and disorders, including anxiety, mood disturbances, fear, schizophrenia, Huntington's chorea, seizures, and epilepsy. GABA receptors' allosteric sites have been demonstrated as highly effective drug targets for mitigating the pathological conditions associated with these brain-related disorders. Exploring the intricacies of GABA receptor subtypes and their complete mechanisms through further studies is essential for identifying novel drug targets and therapeutic strategies for effective management of GABA-related neurological conditions.
5-HT, a neurotransmitter better known as serotonin, fundamentally influences diverse physiological processes throughout the body, ranging from psychoemotional regulation and sensory experiences to blood circulation, food consumption, autonomic functions, memory formation, sleep, and pain perception. G protein subunits' interaction with a spectrum of effectors brings forth a variety of cellular responses, encompassing the inhibition of adenyl cyclase and the modulation of calcium and potassium ion channel activity. selleck inhibitor Protein kinase C (PKC), a second messenger, is activated by signaling cascades. This activation, in turn, disrupts G-protein-dependent receptor signaling, ultimately causing the internalization of 5-HT1A receptors. Subsequent to internalization, the 5-HT1A receptor interacts with the Ras-ERK1/2 pathway. The receptor subsequently undergoes trafficking to the lysosome for the purpose of degradation. The receptor's trafficking route deviates from lysosomal compartments, enabling dephosphorylation. Back to the cell membrane travel the receptors, now devoid of phosphate groups. The internalization, trafficking, and signaling of the 5-HT1A receptor are examined in this chapter.
GPCRs, the largest family of plasma membrane-bound receptor proteins, participate in a wide range of cellular and physiological functions. These receptors undergo activation in response to the presence of extracellular stimuli, including hormones, lipids, and chemokines. Aberrant GPCR expression and genetic alterations contribute to a spectrum of human diseases, encompassing cancer and cardiovascular disease. GPCRs, a rising star as potential therapeutic targets, are receiving attention with many drugs either FDA-approved or undergoing clinical trials. Within this chapter, an update on GPCR research is presented, alongside its critical significance as a therapeutic target.
A lead ion-imprinted sorbent, Pb-ATCS, was formed using the ion-imprinting method with an amino-thiol chitosan derivative as the starting material. The process commenced with the amidation of chitosan by the 3-nitro-4-sulfanylbenzoic acid (NSB) unit, and the subsequent selective reduction of the -NO2 groups into -NH2. Cross-linking of the amino-thiol chitosan polymer ligand (ATCS) with Pb(II) ions, using epichlorohydrin as the cross-linking agent, followed by the removal of the lead ions, led to the desired imprinting. The sorbent's aptitude for selectively binding Pb(II) ions was tested, following an investigation of the synthetic steps using nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR). A capacity for absorbing roughly 300 milligrams of lead (II) ions per gram was observed in the Pb-ATCS sorbent produced, which demonstrated a greater affinity for these ions in comparison to the control NI-ATCS sorbent. media literacy intervention In line with the sorbent's quite rapid adsorption kinetics, the pseudo-second-order equation proved a suitable model. The introduced amino-thiol moieties facilitated the chemo-adsorption of metal ions onto the Pb-ATCS and NI-ATCS solid surfaces, which was shown.
The natural biopolymer starch is remarkably well-suited as an encapsulating agent in nutraceutical delivery systems, exhibiting advantages in its widespread availability, versatility, and remarkable biocompatibility. This review details the recent breakthroughs in the creation of novel starch-based drug delivery systems. A foundational examination of starch's structural and functional roles in the encapsulation and delivery of bioactive ingredients is presented initially. Starch's structural modification empowers its functionalities and extends its range of uses in novel delivery platforms.