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ISRIB
ISRIB (integrated stress response inhibitor) is an experimental drug that reverses the effects of eIF2α phosphorylation with an IC50 of 5 nM. It was discovered in the laboratory of Peter Walter at University of California, San Francisco (UCSF) through a semi-automated screening of a large library of small molecules by Carmela Sidrauski, who decided to pursue research on it.Piore, Adam, The miracle molecule that could treat brain injuries and boost your fading memory', MIT Technology Review, August 25, 2021 (Carmela Sidrauski interview) It has been shown to inhibit eIF2α phosphorylation-induced stress granule (SG) formation. Since eIF2α phosphorylation is known to be involved in memory formation, ISRIB was tested to see whether it would be active ''in vivo'', and was found to readily cross the blood–brain barrier, with a half-life of eight hours. Subsequent testing in 2013 found ISRIB to produce significant nootropic effects in mice, as measured by enhancement of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Integrated Stress Response
The integrated stress response is a cellular stress response conserved in eukaryotic cells that downregulates protein synthesis and upregulates specific genes in response to internal or environmental stresses. Background The integrated stress response can be triggered within a cell due to either extrinsic or intrinsic conditions. Extrinsic factors include hypoxia, amino acid deprivation, glucose deprivation, viral infection and presence of oxidants. The main intrinsic factor is endoplasmic reticulum stress due to the accumulation of unfolded proteins. It has also been observed that the integrated stress response may trigger due to oncogene activation. The integrated stress response will either cause the expression of genes that fix the damage in the cell due to the stressful conditions, or it will cause a cascade of events leading to apoptosis, which occurs when the cell cannot be brought back into homeostasis. eIF2 protein complex Stress signals can cause protein kinase ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nootropic
Nootropics ( , or ) (colloquial: smart drugs and cognitive enhancers, similar to adaptogens) are a wide range of natural or synthetic dietary supplement, supplements or drugs and other substances that are claimed to improve cognitive function or to promote Relaxation (psychology), relaxation, particularly boosting mood, executive functions, attention, memory, creativity, or motivation in healthy individuals. The use of cognition-enhancing supplements by healthy individuals in the absence of a medical indication spans numerous controversial issues, including the Medical ethics, ethics and fairness of their use, concerns over adverse effects, and the drug diversion, diversion of prescription drugs for non-medical uses. Nonetheless, the international sales of cognitive- or mood-enhancing supplements have continued to grow over time and in 2012 reached 0.69 billion. With sales supported by global health trends, the market is expected to reach US$33.85 billion by the year 2030, at ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Meclofenoxate
Meclofenoxate ( INN, BAN; brand name Lucidril, also known as centrophenoxine) is a cholinergic nootropic used as a dietary supplement. It is an ester of dimethylethanolamine (DMAE) and 4-chlorophenoxyacetic acid (pCPA). In elderly patients, meclofenoxate has been shown to improve performance on certain memory tests. Meclofenoxate also increases cellular membrane phospholipids. It is sold in Japan and some European countries, such as Germany, Hungary, and Austria, as a prescription drug. Side effects Meclofenoxate is considered to be very safe and high in tolerability. However, possible side effects may include, rarely, insomnia, dizziness, restlessness, muscle tremor, depression, nausea, muscle tension, and headache; these side effects may be due to overdosage and may indicate the need for the dosage to be reduced. Research Meclofenoxate, as well as DMAE, have been found to increase the lifespans of mice by 26.5%. Brand names In addition to Lucidril, meclofenoxate has al ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chloroarenes
In organic chemistry, an aryl halide (also known as haloarene) is an aromatic compound in which one or more hydrogen atoms, directly bonded to an aromatic ring are replaced by a halide. The haloarene are different from haloalkanes because they exhibit many differences in methods of preparation and properties. The most important members are the aryl chlorides, but the class of compounds is so broad that there are many derivatives and applications. Preparation The two main preparatory routes to aryl halides are direct halogenation and via diazonium salts. Direct halogenation In the Friedel-Crafts halogenation, Lewis acids serve as catalysts. Many metal chlorides are used, examples include iron(III) chloride or aluminium chloride. The most important aryl halide, chlorobenzene is produced by this route. Monochlorination of benzene is always accompanied by formation of the dichlorobenzene derivatives. Arenes with electron donating groups react with halogens even in the absence of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Salubrinal
Salubrinal is a drug which acts as a specific inhibitor of eIF2α phosphatase enzymes and is primarily used experimentally, to study stress responses in eukaryotic cells associated with the action of eIF2. Salubrinal indirectly inhibits eIF2 as a result of reduced dephosphorylation of its α-subunit, resulting in activation of stress response pathways usually triggered by events such as oxidative stress or buildup of unfolded protein in the endoplasmic reticulum. Salubrinal has putative therapeutic value due to its function, but is as yet only used experimentally. Salubrinal is being studied at Indiana University for its potential to fight osteoporosis and accelerate bone healing. References {{Reflist, refs= {{cite journal , vauthors = Kessel D , title = Protection of Bcl-2 by salubrinal , journal = Biochemical and Biophysical Research Communications , volume = 346 , issue = 4 , pages = 1320–3 , date = August 2006 , pmid = 16806073 , pmc = 2978664 , doi = 10.1016/ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
United Press International
United Press International (UPI) is an American international news agency whose newswires, photo, news film, and audio services provided news material to thousands of newspapers, magazines, radio and television stations for most of the 20th century. At its peak, it had more than 6,000 media subscribers. Since the first of several sales and staff cutbacks in 1982, and the 1999 sale of its broadcast client list to its main U.S. rival, the Associated Press, UPI has concentrated on smaller information-market niches. History Formally named United Press Associations for incorporation and legal purposes, but publicly known and identified as United Press or UP, the news agency was created by the 1907 uniting of three smaller news syndicates by the Midwest newspaper publisher E. W. Scripps. It was headed by Hugh Baillie (1890–1966) from 1935 to 1955. At the time of his retirement, UP had 2,900 clients in the United States, and 1,500 abroad. In 1958, it became United Press Int ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Calico (company)
Calico Life Sciences LLC is an Alphabet subsidiary responsible for health research and development, life sciences and biotechnology. Originating on September 18, 2013 prior to the Google restructuring and headed by Bill Maris with the goal of combating aging and diseases of aging, it was incorporated into Alphabet with Google's other sister divisions in 2015. In Google's 2013 Founders Letter, Larry Page described Calico as a company focused on "health, well-being, and longevity" and the company's name additionally as a play on "California Life Company." Partnerships and staff In September 2014, it was announced that Calico, in partnership with AbbVie, would be opening up an R&D facility focused on aging and age-related diseases, such as neurodegeneration and cancer. Initially, each company will invest $350 million, with an option for each to add an extra $500 million later on. In the same month, Calico announced a partnership with the University of Texas Southwestern ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Water Maze (neuroscience)
A water maze is a device used to test an animal's memory in which the alleys are filled with water, providing a motivation to escape. Many different mazes exist, such as T- and Y-mazes, Cincinnati water mazes, and radial arm mazes. Water mazes have been used to test discrimination learning and spatial learning abilities. The Morris water navigation task is often called a "water maze task", but this is erroneous as it is not, properly speaking, a maze. The development of these mazes has aided research into, for example, hippocampal synaptic plasticity In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. Since memories are postulated to be represented by vastly interconnected neural circuits ..., NMDA receptor function, and looking into neurodegenerative diseases, such as Alzheimer's disease. References Behavioral neuroscience {{Neuroscience-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Blood–brain Barrier
The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where neurons reside. The blood–brain barrier is formed by endothelial cells of the capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. This system allows the passage of some small molecules by passive diffusion, as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose and amino acids that are crucial to neural function. The blood–brain barrier restricts the passage of pathogens, the diffusion of solutes in the blood, and large or hydrophilic molecules into the cerebrospinal fluid, while allowing the diffusion of hydrophobic molecules (O2, CO2, hormones) and small non-polar molecules. Cells of the barrier ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EIF2S1
Eukaryotic translation initiation factor 2 subunit 1 (eIF2α) is a protein that in humans is encoded by the ''EIF2S1'' gene. Function The protein encoded by this gene is the alpha (α) subunit of the translation initiation factor eIF2 protein complex which catalyzes an early regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA (Met-tRNAiMet) to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, eIF2, and GTP. eIF2 is composed of 3 nonidentical subunits, alpha (α, 36 kD, this article), beta (β, 38 kD), and gamma (γ, 52 kD). The rate of formation of the ternary complex is modulated by the phosphorylation state of eIF2α. Phosphorylation of eIF2α by EIF-2 kinases plays a key role in regulating the integrated stress response. Clinical significance After reperfusion following brain ischemia, there is inhibition of neuron protein synthesis due to phosphorylation of eIF2α. There is colocalization betwee ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Stress Granule
Stress granules are dense aggregations in the cytosol composed of proteins and RNAs that appear when the cell is under stress. The RNA molecules stored are stalled translation pre-initiation complexes: failed attempts to make protein from mRNA. Stress granules are 100–200 nm in size (when biochemically purified), not surrounded by membrane, and associated with the endoplasmatic reticulum. Note that there are also nuclear stress granules. This article is about the cytosolic variety. Proposed functions The function of stress granules remains largely unknown. Stress granules have long been proposed to have a function to protect RNAs from harmful conditions, thus their appearance under stress. The accumulation of RNAs into dense globules could keep them from reacting with harmful chemicals and safeguard the information coded in their RNA sequence. Stress granules might also function as a decision point for untranslated mRNAs. Molecules can go down one of three paths: fu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
University Of California, San Francisco
The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California. It is part of the University of California system and is dedicated entirely to health science and life science. It conducts research and teaching in medical and biological sciences. UCSF was founded as Toland Medical College in 1864. in 1873, it became affiliated with the University of California as its Medical Department. In the same year, it incorporated the California College of Pharmacy and in 1881 it established a dentistry school. Its facilities were located in both Berkeley and San Francisco. In 1964, the school gained full administrative independence as a campus of the UC system, headed by its own chancellor, and in 1970 it gained its current name. Historically based at Parnassus Heights with satellite facilities throughout the city, UCSF developed a second major campus in the newly redeveloped Mission Bay district in the early 2000s. '' U.S. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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