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Progerin
Progerin (UniProt# P02545-6) is a truncated version of the lamin A protein involved in the pathology of Hutchinson–Gilford progeria syndrome. Progerin is most often generated by a sporadic single point nucleotide polymorphism c.1824 C>T (GGC -> GGT, p.Gly608Gly) in the gene that codes for matured Lamin A. This mutation activates a cryptic splice site that induces a mutation in premature Lamin A with the deletion of a 50 amino acids group near the C-terminus. The endopeptidase ZMPSTE24 cannot cleave between the missing RSY - LLG amino acid sequence (as seen in the figure) during the maturation of Lamin A, due to the deletion of the 50 amino acids which included that sequence. This leaves the intact premature Lamin A bonded to the methylated carboxyl farnesyl group creating the defective protein Progerin, rather than the desired protein matured Lamin A. Approximately 90% of all Hutchinson–Gilford progeria syndrome cases are heterozygous for this deleterious single nucleotide polymo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hutchinson–Gilford Progeria Syndrome
Progeria is a specific type of progeroid syndrome, also known as Hutchinson–Gilford syndrome. A single gene mutation is responsible for progeria. The gene, known as lamin A (LMNA), makes a protein necessary for holding the Nucleus of the cell together. When this gene gets mutated an abnormal form of lamin A protein called Progerin is produced. Progeroid syndromes are a group of diseases that causes individuals to age faster than usual, leading to them appearing older than they actually are. Patients born with progeria typically live to an age of mid-teens to early twenties. Severe cardiovascular complications usually develop by puberty, resulting in death. Signs and symptoms Children with progeria usually develop the first symptoms during their first few months of life. The earliest symptoms may include a failure to thrive and a localized scleroderma-like skin condition. As a child ages past infancy, additional conditions become apparent, usually around 18–24 months. Limite ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lamin A
Pre-lamin A/C or lamin A/C is a protein that in humans is encoded by the ''LMNA'' gene. Lamin A/C belongs to the lamin family of proteins. Function In the setting of ZMPSTE24 deficiency, the final step of lamin processing does not occur, resulting in an accumulation of farnesyl-prelamin A. In Hutchinson–Gilford progeria syndrome, a 50-amino acid deletion in prelamin A (amino acids 607–656) removes the site for the second endoproteolytic cleavage. Consequently, no mature lamin A is formed, and a farnesylated mutant prelamin A (progerin) accumulates in cells. The nuclear lamina consist of a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate la ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lonafarnib
Lonafarnib, sold under the brand name Zokinvy, is a medication used to reduce the risk of death due to Hutchinson-Gilford progeria syndrome and for the treatment of certain processing-deficient progeroid laminopathies in people one year of age and older. The most common side effects included nausea vomiting, headache, diarrhea, infection, decreased appetite and fatigue. Lonafarnib was approved for medical use in the United States in November 2020, and in the European Union in July 2022. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical uses Lonafarnib is indicated to be used to reduce the risk of death due to Hutchinson-Gilford progeria syndrome and for the treatment of certain other processing-deficient progeroid laminopathies in people one year of age and older. Contraindications Lonafarnib is contraindicated for co-administration with strong or moderate CYP3A inhibitors and inducers, as well as midazolam and certain c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ionizing Radiation
Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel up to 99% of the speed of light, and the electromagnetic waves are on the high-energy portion of the electromagnetic spectrum. Gamma rays, X-rays, and the higher energy ultraviolet part of the electromagnetic spectrum are ionizing radiation, whereas the lower energy ultraviolet, visible light, nearly all types of laser light, infrared, microwaves, and radio waves are non-ionizing radiation. The boundary between ionizing and non-ionizing radiation in the ultraviolet area is not sharply defined, as different molecules and atoms ionize at different energies. The energy of ionizing radiation starts between 10 electronvolts (eV) and 33 eV. Typical ionizing subatomic particles include alpha particles, beta particles, and neutrons. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ageing
Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In a broader sense, ageing can refer to single cells within an organism which have ceased dividing, or to the population of a species. In humans, ageing represents the accumulation of changes in a human being over time and can encompass physical, psychological, and social changes. Reaction time, for example, may slow with age, while memories and general knowledge typically increase. Ageing increases the risk of human diseases such as cancer, Alzheimer's disease, diabetes, cardiovascular disease, stroke and many more. Of the roughly 150,000 people who die each day across the globe, about two-thirds die from age-related causes. Current ageing theories are assigned to the damage concept, whereby the accumulation of damage (such as DNA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Rapamycin
Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, and treat perivascular epithelioid cell tumor ( PEComa). It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It is a mechanistic target of rapamycin kinase (mTOR) inhibitor that inhibits activation of T cells and B cells by reducing their sensitivity to interleukin-2 (IL-2). It is produced by the bacterium ''Streptomyces hygroscopicus'' and was isolated for the first time in 1972, from samples of ''Streptomyces hygroscopicus'' found on Easter Island. The compound was originally named rapamycin after the native name of the island, Rapa Nui. Sirolimus was initially developed as an antifungal agent. However, this use was abandoned when it was discovered to have potent im ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Farnesyltransferase Inhibitor
The farnesyltransferase inhibitors (FTIs) are a class of experimental cancer drugs that target protein farnesyltransferase with the downstream effect of preventing the proper functioning of the Ras (protein), which is commonly abnormally active in cancer. Background Studies have suggested that interference with certain post-translational modification processes seem to have quite a high selectivity for targeting cells displaying tumour phenotypes, although the reason for this is a matter of controversy. After translation, Ras goes through four steps of modification: isoprenylation, proteolysis, methylation and palmitoylation. Isoprenylation involves the enzyme farnesyltransferase (FTase) transferring a farnesyl group from farnesyl pyrophosphate (FPP) to the pre-Ras protein. Also, a related enzyme geranylgeranyltransferase I (GGTase I) has the ability to transfer a geranylgeranyl group to K and N-Ras (the implications of this are discussed below). Farnesyl is necessary to attach R ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA Damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages (interstrand crosslinks or ICLs). This can eventually lead to mali ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cell Membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the extracellular space). The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols (a lipid component) interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of cells and organelles, being selectively permeable to io ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (GGU, GGC, GGA, GGG). Glycine is integral to the formation of alpha-helices in secondary protein structure due to its compact form. For the same reason, it is the most abundant amino acid in collagen triple-helices. Glycine is also an inhibitory neurotransmitter – interference with its release within the spinal cord (such as during a ''Clostridium tetani'' infection) can cause spastic paralysis due to uninhibited muscle contraction. It is the only achiral proteinogenic amino acid. It can fit into hydrophilic or hydrophobic environments, due to its minimal side chain of only one hydrogen atom. History and etymology Glycine was discovered in 1820 by the French chemist ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nuclear Lamina
The nuclear lamina is a dense (~30 to 100 nm thick) fibrillar network inside the nucleus of eukaryote cells. It is composed of intermediate filaments and membrane associated proteins. Besides providing mechanical support, the nuclear lamina regulates important cellular events such as DNA replication and cell division. Additionally, it participates in chromatin organization and it anchors the nuclear pore complexes embedded in the nuclear envelope. The nuclear lamina is associated with the inner face of the inner nuclear membrane of the nuclear envelope, whereas the outer face of the outer nuclear membrane is continuous with the endoplasmic reticulum. The nuclear lamina is similar in structure to the nuclear matrix, that extends throughout the nucleoplasm. Structure and composition The nuclear lamina consists of two components, lamins and nuclear lamin-associated membrane proteins. The lamins are type V intermediate filaments which can be categorized as either A-type ( ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gene Conversion
Gene conversion is the process by which one DNA sequence replaces a homologous sequence such that the sequences become identical after the conversion event. Gene conversion can be either allelic, meaning that one allele of the same gene replaces another allele, or ectopic, meaning that one paralogous DNA sequence converts another. Allelic gene conversion Allelic gene conversion occurs during meiosis when homologous recombination between heterozygotic sites results in a mismatch in base pairing. This mismatch is then recognized and corrected by the cellular machinery causing one of the alleles to be converted to the other. This can cause non-Mendelian segregation of alleles in germ cells. Nonallelic/ectopic gene conversion Recombination occurs not only during meiosis, but also as a mechanism for repair of double-strand breaks (DSBs) caused by DNA damage. These DSBs are usually repaired using the sister chromatid of the broken duplex and not the homologous chromosome, so they w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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