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Molecular Biology and Gene Therapy
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
Each DNA molecule is packaged into a chromosome by complex folding of the DNA around proteins. Diploid human cells contain 22 pairs and a pair of sex chromosomes (XX or XY) that determines the sex of the organism. One of each pair of chromosomes is maternally inherited and the other is paternally inherited. The ends of the chromosomes are capped by telomeres, which are specialised structures that are involved in cell mortality. During normal cell division, DNA replication is achieved by the separation of the two strands by DNA helicase. Each separated single strand then acts as a template for forming a new complementary strand.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
RNA folding follows a hierarchical pathway analogous to that observed for proteins. The primary base sequence dictates the type of secondary structure formed, which in turn allows the formation of a possible tertiary structure via interaction of preformed secondary structures. Formation of RNA secondary structure dominates the free energy of folding, as each base pair contributes 1–3 kcal/mol of free energy to the final fold. For example, transfer RNAs (tRNAs) have a uniquely evolved tertiary structure, and their primary sequence directs a “clover leaf” secondary structure composed of three stem-loop segments. However, the well-known three-dimensional structure of tRNAs is finalized by the interaction between two of the hairpin loops (the T- and C-loops). This last step, the formation of tertiary structure, contributes only 1.5 kcal/mol of free energy. With regard to small molecule targeting, the secondary structure is generally regarded as the key determinant in defining the “druggability” of a particular RNA.
A Treatise on the Role of Herpesvirus in Neurodegeneration
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Bernard W. Downs, Manashi Bagchi, Bruce S. Morrison, Jeffrey Galvin, Steve Kushner, Debasis Bagchi, Kenneth Blum
The current prevailing thought is that neurodegenerative diseases are caused for the most part by abnormalities in the processing of proteins [26]. In each of these diseases, misfolding and processing of proteins (i.e., “prions”) triggers normal proteins in the brain to also fold abnormally by some idiopathic mechanism, on which we will proffer a hypothesis based on evidence. This abnormal folding causes the accumulation of one or more specific neuronal proteins, which characterize several fatal and transmissible neurodegenerative diseases in humans. To reiterate, published research indicates that autoimmunity is more accurately defined as an upregulated immune response (which is not necessarily an error) to a perceived antigen, such as an imperfectly synthesized, formed, and/or shaped molecule, or component of a glycoprotein [24]. But what is causing this malformation of glycoprotein structures? Is it a deficiency in a molecular component or an inability to implant a molecular component due to an enzyme deficiency or mineral deficiency causing a disruption to enzyme function? In any event, there is a malformation of a molecular structure, which impairs the function and induces an upregulated immune intervention.
Strategies for targeting RNA with small molecule drugs
Published in Expert Opinion on Drug Discovery, 2023
Christopher L. Haga, Donald G. Phinney
Several methods have been developed to experimentally determine the secondary structure folding of RNA. These methods largely focus on determining regions of RNA susceptible to attack or modification by nucleases, chemical reagents, or electrophiles, thereby identifying the solvent-exposed regions of the RNA structure (Figure 2) [18]. Early experimentation in determining RNA structures was carried out via enzymatic mapping via specific endonucleases that cleave single-stranded RNA regions without sequence preference [19]. These experiments relied on hydrolysis of radioactively labeled RNA generating a specific cleavage pattern which was then directly analyzed by gel electrophoresis or by detecting reverse transcription stops of cleaved products by Sanger sequencing [20]. However, due to local steric hindrance effects and the possibility that nucleotides may be obscured by RNA tertiary structures, enzymatic reactions are infeasible for practical and accurate probing of RNA secondary structures at the level of the transcriptome.
Nano-lipidic formulation and therapeutic strategies for Alzheimer’s disease via intranasal route
Published in Journal of Microencapsulation, 2021
Shourya Tripathi, Ujala Gupta, Rewati Raman Ujjwal, Awesh K. Yadav
The most common striking feature that AD has in common with other neurodegenerative diseases is the abnormal folding of proteins. Talking specifically about AD, there is aberrant production of proteins at intracellular and extracellular levels inside the brain. Neurofibrillary tangles are found to increase at the intracellular level whereas amyloid plaques are seen at the extracellular level. There exist many factors behind the origin of AD and one of the widest acclaimed hypothesis behind the abnormal plaque formation is the amyloid cascade hypothesis (Dá Mesquita et al.2016). As for the genetic cause, disease genes that undergo mutation include those encoding presenilin 1 on chromosome 14q24 (PSEN1), presenilin 2 on chromosome 1q42 (PSEN2), and amyloid precursor protein (APP) on chromosome 21q21. These are also known as ‘causative genes’ and are responsible for nearly 5% of AD cases occurring on a totality (Imbimbo et al.2005). Figure 1 portrays the pathophysiology involved in AD.
The ameliorating approach of nanorobotics in the novel drug delivery systems: a mechanistic review
Published in Journal of Drug Targeting, 2021
Rakesh K. Sindhu, Harnoor Kaur, Manish Kumar, Moksha Sofat, Evren Algın Yapar, Imren Esenturk, Bilge Ahsen Kara, Pradeep Kumar, Zakieh Keshavarzi
The introduction of DNA origami automation which come up with new ways for studies of manufacturing nanorobots [58]. In 2006, DNA origami was originated [59]. It is a DNA-formed technology that takes advantage of an organised coalition of hundreds of short corresponding ‘staple’ oligonucleotides which can form précised 2D and 3D structures by folding a huge solitary filament of ‘scaffold’ DNA which are sustained by many base pairs [60]. DNA origami is used as a broad-spectrum for effective stability of nanostructures and high powdered nanodevices which are fabricated, preparing the way for DNA nanorobotics [61]. Lund et al. [62] in 2010 come along with operating robotic behaviours of DNA walkers which is made up of streptavidin molecule on the substratum molecules lined up on 2D DNA origami landscape, showing the attainability of organised behaviour of robots relied on DNA automation. Various evaluation results evidence that the robotic automated actions have become remarkably rapid than earlier appeared DNA motor systems and biohybrids which are powered by the adenosine triphosphates. Studies also demonstrate that at two-dimensional DNA crystalline substrate, DNA nanorobots can be inserted at particular sites [63] and type of took up, locate and drop off contents [64]. These outcomes appreciably signify the considerable ability of DNA origami technology in nanorobotic processes.