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Climate change is a change in the usual weather found in a place. The climate change has a major impact not only on natural disasters of the Earth but also on human health. The climate crisis is then no longer a future concern. It includes both the global warming driven by human emissions of greenhouse gases (GHG), and the resulting large-scale shifts in weather patterns. Global warming can occur from a variety of causes, both natural and human induced. The primary GHG in Earth's atmosphere, listed in decreasing order of average global mole fraction, are: water vapor (H2O), carbon dioxide (CO2), methane (CH4), nitrous oxide (N2O), and ozone (O3). Today, scientists around the world continue to try and solve the puzzle of climate change. It is clear that to address climate change, the amount of CO2 released into the atmosphere by industrial process has to be reduced because once it is added to the atmosphere, it can continue to affect climate for thousands of years. For such a purpose, an approach to intervention using expression vectors for any protein targeting to the cell plasma membrane via the glycosylphosphatidylinositol, GPI, anchor is suggested. The resulting GPI-anchored proteins would be useful for studying intermolecular interactions, especially gene-environment interactions, in investigating the potential impact of any chemical compounds on any genes of interest and could be used for carbonic anhydrase (CA)-based CO2-capture (environmental application). This approach would be crucial not only for capturing CO2via GPI and CA but also for the production of CA enzyme as well as its stabilization and therefore useful for combating the global warming of climate change. [ABSTRACT FROM AUTHOR]

Beta-amyloid precursor protein (APP) is a membrane-spanning protein with a large extracellular domain and a much smaller intracellular domain. APP plays a central role in Alzheimer’s disease (AD) pathogenesis: APP processing generates β-amyloid (Aβ) peptides, which are deposited as amyloid plaques in the brains of AD individuals; point mutations and duplications of APP are causal for a subset of early-onset familial AD (FAD) (onset age 65 years old), and the pathophysiology of this disorder is not yet fully understood. APP is an extremely complex molecule that may be functionally important in its full-length configuration, as well as the source of numerous fragments with varying effects on neural function, yet the normal function of APP remains largely unknown. This article provides an overview of our current understanding of APP, including its structure, expression patterns, proteolytic processing and putative functions. Importantly, and for the first time, my recent data concerning its epigenetic regulation, especially in alternative APP pre-mRNA splicing and in the control of genomic rearrangements of the APP gene, are also reported. These findings may provide new directions for investigating the role of APP in neuropathology associated with a deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt) found in patients with Lesch-Nyhan syndrome (LNS) and its attenuated variants (LNVs). Also, these findings may be of significance for research in neurodevelopmental and neurodegenerative disorders in which the APP gene is involved in the pathogenesis of diseases such as autism, fragile X syndrome (FXS) and AD, with its diversity and complexity, SAD in particular. Accurate quantification of various APP-mRNA isoforms in brain tissues is needed, and antisense drugs are potential treatments.

Several pathophysiological functions of the human β-amyloid precursor protein (APP) have been recently proposed in different human diseases such as neurodevelopmental and neurodegenerative disorders including rare diseases such as autism, fragile X syndrome, amyotrophic lateral sclerosis, multiple sclerosis, Lesch-Nyhan disease; common and complex disorders such as Alzheimer's disease; metabolic disorders such as diabetes; and also cancer. APP as well as all of its proteolytic fragments including the amyloid-β (Aβ) peptide, are part of normal physiology. The targeting of the components of APP proteolytic processing as a pharmacologic strategy will not be without consequences. Recent research results highlight the impact of alternative splicing (AS) process on human disease, and may provide new directions for the research on the impact of the human APP on human diseases. The identification of molecules capable of correcting and/or inhibiting pathological splicing events is therefore an important issue for future therapeutic approaches. To this end, the defective APP-mRNA isoform responsible for the disease in cells and tissues appears as an ideal target for epigenetic therapeutic intervention and antisense drugs are potential treatment. [ABSTRACT FROM AUTHOR]

Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorders of purine metabolic in which the cytoplasmic enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. Despite having been characterized over 60 years ago, however, up to now, there is no satisfactory explanation of how deficits in enzyme HGprt can lead to LND with the development of the persistent and severe self-injurious behavior. Recently, a role for epistasis between the mutated hypoxanthine phosphoribosyltransferase 1 ( HPRT1 ) and the β-amyloid precursor protein (APP) genes affecting the regulation of alternative APP pre-mRNA splicing in LND has been demonstrated. Furthermore, there were also some reported cases of LND developing thrombosis while APP is an important regulator of vein thrombosis and controls coagulation. Otherwise, the surface expression of HGprt enzyme was also observed in several somatic tissue cancers while APP and the APP-like protein-2 (APLP2) are deregulated in cancer cells and linked to increased tumor cell proliferation, migration, and invasion. The present review provides a discussion about these findings and suggests a potential molecular link between APP and HGprt via epistasis between HPRT1 and APP genes affecting the regulation of alternative APP pre-mRNA splicing. As a perspective, expression vectors for HGprt enzyme and APP are constructed as described in Ref. # 24 (Nguyen KV, Naviaux RK, Nyhan WL (2020) Lesch-Nyhan disease: I. Construction of expression vectors for hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme and amyloid precursor protein (APP). Nucleosides Nucleotides Nucleic Acids 39: 905-922), and they could be used as tools for clarification of these issues. In addition, these expression vectors, especially the one with the glycosyl-phosphatidylinositol (GPI) anchor can be used as a model for the construction of expression vectors for any protein targeting to the cell plasma membrane for studying intermolecular interactions and could be therefore useful in the vaccines as well as antiviral drugs development (studying intermolecular interactions between the spike glycoprotein of the severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, as well as its variants and the angiotensin-converting enzyme 2, ACE2, in coronavirus disease 2019 (COVID-19) [43],[44], for example)., Competing Interests: Conflict of interest: The author declares that there are no conflicts of interest., (© 2021 the Author(s), licensee AIMS Press.)

beta-Amyloid peptide (beta A) is a major fibrillar component of neuritic plaques in Alzheimer's disease (AD) brains and is related to the pathogenesis of the disease. In this study, using electron microscopy, we describe herein the results concerning the efficacy of compounds that can dissolve preformed beta A fibrils in vitro. For such a purpose, two hydrosoluble and biocompatible polymers such as polyethylene glycol and poly-L-lysine were used. The poly-L-lysine appears as a potent dissolver of preformed beta A fibrils in vitro. Its efficiency is instantaneous. Poly-L-lysine can be used as a universal dissolver of all types of oligomeric beta-sheet conformation, precursor of the fibrils. This finding provides the basis for future investigation of the therapeutic potential of poly-L-lysine in terms of preventing and/or retarding amyloidogenesis in AD and other types of amyloid-related disorders.