This chapter investigates the fundamental processes of amyloid plaque formation, cleavage, structural characteristics, expression patterns, diagnostic tools, and potential therapeutic strategies for Alzheimer's disease.
The hypothalamic-pituitary-adrenal (HPA) axis and extrahypothalamic neural pathways rely on corticotropin-releasing hormone (CRH) for basal and stress-activated processes, where it acts as a neuromodulator to coordinate behavioral and humoral reactions to stress. A review of cellular components and molecular mechanisms of CRH system signaling through G protein-coupled receptors (GPCRs) CRHR1 and CRHR2 is presented, drawing on current models of GPCR signaling within both plasma membrane and intracellular compartments, establishing the basis of signal resolution in space and time. Recent investigations into CRHR1 signaling within physiologically relevant neurohormonal contexts have shed light on novel mechanisms impacting cAMP production and ERK1/2 activation. The pathophysiological function of the CRH system is also briefly reviewed, stressing the need for a full elucidation of CRHR signaling to allow the creation of new and specific therapeutic approaches for stress-related disorders. Our overview is brief.
Ligand-binding characteristics categorize nuclear receptors (NRs), the ligand-dependent transcription factors, into seven superfamilies, ranging from subgroup 0 to subgroup 6. Simufilam NRs, without exception, exhibit a consistent domain structure (A/B, C, D, and E), each segment playing a distinct and essential role. Hormone Response Elements (HREs) serve as binding sites for NRs, which exist as monomers, homodimers, or heterodimers. Nuclear receptor binding is also impacted by slight variations in the sequences of the HREs, the gap between the half-sites, and the surrounding DNA sequence of the response elements. NRs are capable of controlling the expression of their target genes, achieving both activation and repression. Positively regulated genes experience activation of target gene expression when nuclear receptors (NRs) are bound to their ligand, thereby recruiting coactivators; unliganded NRs induce transcriptional repression, instead. In contrast, gene silencing by NRs occurs through two separate mechanisms: (i) transcriptional repression reliant on ligands, and (ii) transcriptional repression independent of ligands. This chapter will offer a succinct account of NR superfamilies, highlighting their structures, molecular mechanisms, and roles in pathophysiological scenarios. The discovery of novel receptors and their ligands, as well as an understanding of their roles in various physiological processes, is potentially achievable through this method. To address the dysregulation of nuclear receptor signaling, therapeutic agonists and antagonists will be developed.
The non-essential amino acid glutamate acts as a principal excitatory neurotransmitter, with a profound impact on the central nervous system's function. This molecule engages with two distinct types of receptors: ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs), which are essential for postsynaptic neuronal excitation. Learning, communication, memory, and neural development are all positively influenced by these factors. Cellular excitation and the modulation of receptor expression on the cell membrane are fundamentally dependent on endocytosis and the receptor's subcellular trafficking. A receptor's type, the presence of ligands, agonists, and antagonists, all significantly influence its endocytosis and trafficking. The intricacies of glutamate receptor subtypes, their types, and the mechanisms controlling their internalization and trafficking are elucidated in this chapter. A brief look at the roles of glutamate receptors is also included in discussions of neurological diseases.
The postsynaptic target tissues, along with neurons, secrete neurotrophins, soluble factors indispensable to the growth and viability of neuronal cells. The processes of neurite growth, neuronal survival, and synaptogenesis are under the control of 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. Thereafter, this intricate system is transported to the endosomal membrane, allowing Trk proteins to initiate subsequent signaling pathways. Co-receptors, endosomal localization, and the expression profiles of adaptor proteins all contribute to Trks' regulation of a wide array of mechanisms. This chapter offers a comprehensive look at the interplay of endocytosis, trafficking, sorting, and signaling in neurotrophic receptors.
GABA, or gamma-aminobutyric acid, is the primary neurotransmitter, exhibiting its inhibitory effect within chemical synapses. Concentrated primarily within the central nervous system (CNS), it maintains a balance between excitatory impulses (which are dictated by the neurotransmitter glutamate) and inhibitory impulses. GABA's activity is mediated by binding to its specific receptors GABAA and GABAB, which occurs after its discharge into the postsynaptic nerve terminal. These receptors are assigned to the tasks of fast and slow neurotransmission inhibition, respectively. By opening chloride channels, the ligand-gated GABAA receptor decreases membrane potential, leading to the inhibition of synaptic transmission. In opposition to the former, the GABAB receptor, a metabotropic kind, increases potassium ion levels, obstructing calcium ion release and therefore hindering the release of additional neurotransmitters from the presynaptic membrane. Internalization and trafficking of these receptors are carried out through unique pathways and mechanisms, which are thoroughly examined in the chapter. The brain's ability to maintain optimal psychological and neurological states depends critically on adequate GABA. Neurodegenerative diseases/disorders, such as anxiety, mood disorders, fear, schizophrenia, Huntington's chorea, seizures, and epilepsy, have been linked to diminished GABA levels. Studies have confirmed that the allosteric sites on GABA receptors are promising therapeutic targets for alleviating the pathological states of brain-related disorders. Comprehensive studies exploring the diverse subtypes of GABA receptors and their intricate mechanisms are needed to discover new therapeutic approaches and drug targets for managing GABA-related neurological conditions.
The neurotransmitter 5-hydroxytryptamine (5-HT), commonly known as serotonin, exerts control over a vast array of bodily functions, ranging from emotional and mental states to sensory input, circulatory dynamics, eating habits, autonomic responses, memory retention, sleep cycles, and pain perception. G protein subunits, by binding to varying effectors, stimulate diverse cellular responses, such as the inhibition of adenyl cyclase and the control of calcium and potassium ion channel opening. Medicine Chinese traditional Signaling cascades, by activating protein kinase C (PKC), a secondary messenger, trigger the detachment of G-protein-coupled receptor signaling and, consequently, the internalization of 5-HT1A receptors. The 5-HT1A receptor, having undergone internalization, now connects with the Ras-ERK1/2 pathway. For degradation, the receptor is ultimately directed to the lysosome. Escaping lysosomal compartments, the receptor proceeds to undergo dephosphorylation. The dephosphorylated receptors are now being transported back to the cell membrane. This chapter investigated the internalization, trafficking, and signaling cascades of the 5-HT1A receptor.
Among the plasma membrane-bound receptor proteins, G-protein coupled receptors (GPCRs) constitute the largest family, influencing a multitude of cellular and physiological actions. The activation of these receptors is a consequence of exposure to extracellular stimuli, such as hormones, lipids, and chemokines. Many human illnesses, like cancer and cardiovascular disease, are connected to the aberrant expression and genetic alterations within GPCRs. Potential therapeutic targets, GPCRs, have witnessed a surge in drug development, with numerous drugs either FDA-approved or currently under clinical investigation. This chapter provides a comprehensive update on GPCR research, showcasing its crucial role as a future therapeutic target.
A lead ion-imprinted sorbent, Pb-ATCS, was developed using an amino-thiol chitosan derivative, via the ion-imprinting technique. Chitosan was amidated with the 3-nitro-4-sulfanylbenzoic acid (NSB) unit as the initial step, and the resulting -NO2 groups were then selectively reduced to -NH2. The amino-thiol chitosan polymer ligand (ATCS) polymer, cross-linked with Pb(II) ions and epichlorohydrin, underwent a process of Pb(II) ion removal, which resulted in the desired imprinting. Investigations into the synthetic steps, utilizing nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR), were undertaken. The sorbent's ability to selectively bind Pb(II) ions was then evaluated. The Pb-ATCS sorbent produced exhibited a peak adsorption capacity of approximately 300 milligrams per gram, demonstrating a stronger attraction to Pb(II) ions compared to the control NI-ATCS sorbent. Uyghur medicine The pseudo-second-order equation effectively described the sorbent's rapid adsorption kinetics. The phenomenon of metal ions chemo-adsorbing onto the Pb-ATCS and NI-ATCS solid surfaces, via coordination with the introduced amino-thiol moieties, was demonstrated.
As a naturally occurring biopolymer, starch is uniquely positioned as a valuable encapsulating material in nutraceutical delivery systems, due to its diverse sources, adaptability, and high degree of biocompatibility. In this review, the latest progress in the development of starch-based delivery systems is carefully laid out. We begin by exploring the structure and functionality of starch in the processes of encapsulating and delivering bioactive ingredients. The structural alteration of starch enhances its functional properties and broadens its utility in innovative delivery systems.