This is a working overview of neurotrophic factor, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2026-03-18. Anything still debated is marked as such rather than presented as settled.
Development took place during the 1980s at institutes of the Russian Academy of Sciences, where peptide fragments of ACTH were screened for cognitive and neuroprotective effects. The compound received regulatory approval in Russia as a nasal preparation, marketed for conditions such as ischemic stroke, transient ischemic attacks, and optic nerve disorders. Registration in other countries has not followed. Most published clinical reports originate from a small number of Russian research groups, and independent replication outside that setting remains limited. The regulatory status therefore differs sharply between Russia and the rest of the world.
Laboratory work points toward modulation of neurotrophic signaling, particularly expression of brain-derived neurotrophic factor and nerve growth factor in hippocampal tissue. Studies also describe effects on monoamine turnover, inflammatory mediators, and oxidative markers. These observations come mainly from animal models and cultured cells, so the causal chain in humans is not firmly established. Whether the reported molecular changes translate into measurable clinical benefit is an open question. Reviews generally present the mechanism as plausible rather than demonstrated.
Clinical evidence consists largely of small trials with modest sample sizes, often without independent replication. Reported endpoints include cognitive scores, recovery after stroke, and visual function, but study designs vary widely and few trials meet contemporary reporting standards. Systematic reviewers have noted a high risk of bias in several of these reports. No large multicenter trial conducted outside Russia has been published. The compound is therefore best described as investigational in most jurisdictions, with its clinical role still unresolved.
Published research covers ischemic stroke, traumatic brain injury, cognitive impairment, optic nerve conditions and attention-related measures. Much of the human evidence comes from small trials conducted in one country, which limits how far the results generalize. Animal models supply the larger share of the data, and effects seen in rodents do not transfer automatically to people. Reviews have noted that methodological reporting is often incomplete, making it difficult to pool results or compare treatment schedules across studies.
Pharmacokinetic accounts emphasize rapid breakdown. After intravenous dosing the intact peptide disappears from blood within minutes, and nasal delivery produces low but measurable concentrations. Metabolites rather than the parent molecule may account for part of the observed activity, although the relative contribution is unresolved. Dosing in the literature varies widely and no optimal schedule has been agreed. These gaps are regularly cited as a reason the findings have not produced broad clinical adoption beyond the original research setting.
Proposed mechanisms center on neurotrophic signaling rather than on classical melanocortin receptor activation. Rodent experiments have reported shifts in the expression of brain-derived neurotrophic factor and nerve growth factor after administration, together with changes in the associated receptor systems. Several authors argue that the peptide acts largely through its degradation products and their interaction with peptidergic pathways, but this remains a hypothesis rather than a settled finding. No single molecular target has been identified in a way that the field broadly accepts.
| Property | Value | Notes |
|---|---|---|
| Sequence | Met-Glu-His-Phe-Pro-Gly-Pro | Heptapeptide; ACTH(4-10) analog extended at C-terminus |
| Molecular mass | ~813.9 Da | Free peptide, unmodified |
| Appearance | White to off-white powder | Typical lyophilized solid |
| Solubility | Soluble in water and saline | Also soluble in common aqueous buffers |
| Storage (solid) | -20 °C, desiccated | Protect from moisture and repeated thawing |
Later generations of the molecule include an N-acetylated form and an amidated form, both marketed online alongside the parent peptide. These variants differ in terminal chemistry and stability, and they are frequently discussed in the same breath even though they have not been compared in controlled trials. Supply outside formal healthcare systems comes largely from laboratories that synthesize peptides to order. Purity and identity of these materials vary widely, and no single body oversees the international trade.
Semax is a synthetic heptapeptide developed in the Soviet Union during the 1980s by researchers at the Institute of Molecular Genetics in Moscow. It was designed as a truncated analog of adrenocorticotropic hormone, retaining only the fragment spanning residues four through ten. Investigators sought a peptide that would preserve the cognitive effects associated with ACTH while eliminating the hormonal stimulation of the adrenal cortex. The compound entered clinical use in Russia during the following decade.
Russian regulatory authorities approved the peptide for nasal administration, and it remains listed in the national pharmacopoeia under several trade names. Documented indications include acute ischemic stroke, transient ischemic attacks, traumatic brain injury, and certain ophthalmological and neurological conditions. Physicians also prescribe it for cognitive complaints in older patients, although the evidence base for that use is thinner. Outside Russia and a few neighboring states, the substance is not an approved medicine and is sold instead as a research chemical.
Purity assessment relies mainly on reversed-phase high-performance liquid chromatography, which separates the target heptapeptide from truncated sequences, deletion analogues, and oxidised forms. Mass spectrometry, usually coupled to liquid chromatography, confirms identity through the expected molecular ion and reveals modifications such as methionine sulfoxide formation. Amino acid analysis can verify composition, and tandem mass spectrometry supports sequence confirmation. Ultraviolet detection near 254 to 280 nanometres is convenient because the phenylalanine and histidine residues absorb in that region. Nuclear magnetic resonance is rarely used for routine release testing.
Common degradation pathways include oxidation of the methionine side chain, hydrolysis of the peptide backbone, and aggregation under unfavourable pH or concentration. Stability studies typically monitor the main peak by chromatography and report total related substances as a percentage. Because no official monograph exists, acceptance criteria vary between laboratories, and reported purity values are not directly comparable across suppliers. Analysts therefore document the method, column, and detection wavelength alongside each result, and open questions remain about how much biological activity the oxidised forms retain.
structural protein Any protein which contributes to the mechanical shape and structure of cells, organelles, or tissues (e.g. collagen and actin), as distinguished from proteins which serve some other purpose, such as enzymes. This distinction is not well-defined, however, as many proteins have both structural and non-structural roles.
The request for a sequel to The Hobbit prompted Tolkien to begin what ultimately developed into his magnum opus: the epic high-fantasy novel The Lord of the Rings. Written in stages and heavily expanded from its original scope, the novel was published in three volumes between 1954 and 1955. Tolkien spent more than ten years writing the primary narrative and appendices for The Lord of the Rings, during which time he received the constant support of the Inklings, in particular his closest friend C. S. Lewis, the author of The Chronicles of Narnia. Both The Hobbit and The Lord of the Rings are set against the background of The Silmarillion, but in a time long after it. Tolkien at first intended The Lord of the Rings to be a children's tale in the style of The Hobbit, but it quickly grew darker and more serious in the writing. Though a direct sequel to The Hobbit, it addressed an older audience, drawing on the immense backstory of Beleriand that Tolkien had constructed in previous years, which eventually saw posthumous publication in The Silmarillion and other volumes. Tolkien strongly influenced the fantasy genre that grew up after the book's success. The Lord of the Rings became immensely popular in the 1960s and has remained so ever since, ranking as one of the most popular works of fiction of the 20th century, judged by both sales and reader surveys. In the 2003 "Big Read" survey conducted by the BBC, The Lord of the Rings was found to be the UK's "Best-loved Novel".
== The formation of multicellularity == The formation of multicellularity was a pivotal point in the evolution of life on Earth. Shortly after multicellularity arose, there was an immense increase in the diversity of living organisms at the beginning of the Cambrian Era, called the Cambrian Explosion. Multicellularity is believed to have evolved multiple times on Earth because it was a beneficial life strategy for organisms. For multicellularity to occur, cells need to be capable of self-replication, cell-cell adhesion and cell-cell communication. There also must have been available oxygen and selective pressures in the environment.
==== Hamaker interaction ==== As nanoparticle interactions take place on a nanoscale, the particle interactions must be scaled similarly. Hamaker interactions take into account the polarization characteristics of a large number of nearby particles and the effects they have on each other. Hamaker interactions sum all of the forces between all particles and the solvent(s) involved in the system. While Hamaker theory generally describes a macroscopic system, the vast number of nanoparticles in a self-assembling system allows the term to be applicable. Hamaker constants for nanoparticles are calculated using Lifshitz theory, and can often be found in literature.
Sources: en.wikipedia.org
=== Assumed correlation between impact factor and quality === The journal impact factor was originally designed by Eugene Garfield as a metric to help librarians make decisions about which journals were worth indexing, as the JIF aggregates the number of citations to articles published in each journal. Since then, the JIF has become associated as a mark of journal "quality", and gained widespread use for evaluation of research and researchers instead, even at the institutional level. It thus has significant impact on steering research practices and behaviors. By 2010, national and international research funding institutions were already starting to point out that numerical indicators such as the JIF should not be considered as a measure of quality. In fact, research was indicating that the JIF is a highly manipulated metric, and the justification for its continued widespread use beyond its original narrow purpose seems due to its simplicity (easily calculable and comparable number), rather than any actual relationship to research quality. Empirical evidence shows that the misuse of the JIF—and journal ranking metrics in general—has a number of negative consequences for the scholarly communication system. These include gaps between the reach of a journal and the quality of its individual papers and insufficient coverage of social sciences and humanities as well as research outputs from across Latin America, Africa, and South-East Asia.
Transdermal estradiol bypasses the intestines and liver and hence the first-pass metabolism that is associated with oral administration. In addition, unlike oral estradiol, transdermal estradiol is not associated with supraphysiological concentrations of estrone or estrogen conjugates like estradiol sulfate, and transdermal estradiol does not have disproportionate effects on liver protein synthesis. In accordance, estradiol, at typical menopausal replacement dosages, has been found not to increase the risk of blood clots or insulin resistance, nor to affect hepatic SHBG, IGF-1, GHBP, IGFBP, and other protein production and by extension circulating hepatic protein levels. However, at higher doses, transdermal estradiol has been associated with a significantly higher incidence of stroke in postmenopausal women, probably due to blood clots. Another larger study did not find a significantly higher risk of blood clots with similar doses of transdermal estradiol however.
=== Androgen signaling === The androgen response mechanism involves androgens binding to androgen receptors in the cytoplasm, which then move into the nucleus and control gene transcription by interacting with specific DNA regions called androgen response elements. This response mechanism is involved in male sexual differentiation and puberty, as well as other tissue types and processes, such as the prostate gland (regulate secretory functions), hair follicles (androgens influence hair growth patterns), skin (androgens regulate sebum production and the thickening and maturation of the skin), and muscle (contribute to the development and maintenance of muscle mass and strength). Such tissues, where androgens exert their effects, are called 'androgen target tissues'. Different androgens have different effects on androgen receptors because they have different degrees of binding and activating the receptors. Physiologically significant androgens are those androgens that have a strong influence on the development and functioning of male sexual characteristics, unlike physiologically insignificant androgens, which have low biological activity or are quickly metabolized into other steroids. Physiologically insignificant androgens do not have a notable influence on the development and functioning of male or female sexual characteristics, they can be products of the metabolism of more active androgens, such as testosterone (T), or their precursors.
Audit management Fully track and maintain an audit trail Barcode handling Assign one or more data points to a barcode format; read and extract information from a barcode Chain of custody Assign roles and groups that dictate access to specific data records and who is managing them Compliance Follow regulatory standards that affect the laboratory Customer relationship management Handle the demographic information and communications for associated clients Document management Process and convert data to certain formats; manage how documents are distributed and accessed Instrument calibration and maintenance Schedule important maintenance and calibration of lab instruments and keep detailed records of such activities Inventory and equipment management Measure and record inventories of vital supplies and laboratory equipment Manual and electronic data entry Provide fast and reliable interfaces for data to be entered by a human or electronic component Method management Provide one location for all laboratory process and procedure (P&P) and methodology to be housed and managed as well as connecting each sample handling step with current instructions for performing the operation Personnel and workload management Organize work schedules, workload assignments, employee demographic information, training, and financial information Quality assurance and control Gauge and control sample quality, corrective and preventive action (CAPA), data entry standards, and workflow Reports Create and schedule reports in a specific format; schedule and distribute reports to designated parties Time tracking Calculate and maintain processing and handling times on chemical reactions, workflows, and more Traceability Show audit trail and/or chain of custody of a sample Workflows Track a sample, a batch of samples, or a "lot" of batches through its lifecycle
=== Approval === On April 1, 2008, Progenics and Wyeth announced that Health Canada has approved methylnaltrexone for the treatment of opioid-induced constipation. It was later approved by the US FDA on April 24, 2008.
Sources: en.wikipedia.org
Whereas testosterone is the major circulating androgen, DHT is the major androgen in the prostate gland. DHT levels in circulation are relatively low and only approximately 10% of those of circulating testosterone levels. Conversely, local concentrations of DHT in the prostate gland are 8- to 10-fold higher than circulating levels of DHT. This is due to high expression of 5α-reductase in the prostate gland, which very efficiently catalyzes the formation of DHT from testosterone such that over 90% of intraprostatic testosterone is converted into DHT. Relative to testosterone, DHT is 2.5- to 10-fold as potent as an AR agonist in bioassays, and hence, is a much stronger androgen in comparison. As such, AR signaling is exceptionally high in the prostate gland, and the effectiveness of bicalutamide monotherapy in the treatment of prostate cancer, which is roughly equivalent to that of gonadotropin-releasing hormone analogues (GnRH analogues), demonstrates a capacity of bicalutamide to strongly antagonize the AR. On the other hand, GnRH analogue monotherapy achieves only a 50 to 60% reduction in levels of DHT in the prostate gland, and combined androgen blockade (CAB), the combination of surgical castration or a GnRH analogue and bicalutamide, is significantly more effective than either modality alone in the treatment of prostate cancer.
Pilot offers treatment for erectile dysfunction, premature ejaculation, hair loss, and weight management. Juniper provides GLP-1 receptor agonist therapy (such as Ozempic, Mounjaro and Wegovy) combined with health coaching for weight management. Software delivers online dermatology consultations and prescription skincare formulations. Kin provides reproductive health services including contraception, fertility support, and pregnancy care. Compound, a men's preventative health program launched in 2024, was paused later that year before relaunching in the UK in 2025. The company reported revenue of A$120.9 million in FY 2024, with 60% generated from international markets.
== Structure == Alpha-synuclein in solution is considered to be an intrinsically disordered protein, i.e. it lacks a single stable 3D structure. As of 2014, an increasing number of reports suggest, however, the presence of partial structures or mostly structured oligomeric states in the solution structure of alpha-synuclein even in the absence of lipids. This trend is also supported by a large number of single molecule (optical tweezers) measurements on single copies of monomeric alpha-synuclein as well as covalently enforced dimers or tetramers of alpha-synuclein. Alpha-synuclein is specifically upregulated in a discrete population of presynaptic terminals of the brain during a period of acquisition-related synaptic rearrangement. It has been shown that alpha-synuclein significantly interacts with tubulin, and that alpha-synuclein may have activity as a potential microtubule-associated protein, like tau. Evidence suggests that alpha-synuclein functions as a molecular chaperone in the formation of SNARE complexes. In particular, it simultaneously binds to phospholipids of the plasma membrane via its N-terminus domain and to synaptobrevin-2 via its C-terminus domain, with increased importance during synaptic activity. Indeed, there is growing evidence that alpha-synuclein is involved in the functioning of the neuronal Golgi apparatus and vesicle trafficking. Apparently, alpha-synuclein is essential for normal development of the cognitive functions.
In January 1821, in expectation of the abolition in Spain of the Constitution of 1812, Iturbide was chosen and was sent by the officials of New Spain with Guerrero, the leader of the rebellions. He began so-called "peace" negotiations, suggesting the parties unite to establish an independent New Spain. Later, Iturbide was dethroned and quietly captured to be executed. The simple terms that Iturbide proposed became the basis of the Plan of Iguala: the independence of New Spain (now to be called the Mexican Empire) with Ferdinand VII or another Bourbon as emperor; the retention of the Catholic Church as the official state religion and the protection of its existing privileges; and the equality of all New Spaniards, whether immigrants or native-born. Many of that laws was abolished decades later or are in present-day Mexico. The following month the other important guerrilla leader, Guadalupe Victoria, joined the alliance, and on 1 March Iturbide was proclaimed head of a new Army of the Three Guarantees. The representative of the new Spanish government, Superior Political Chief Juan O'Donojú, who replaced the previous viceroys, arrived in Veracruz on 1 July 1821, but he found that royalists held the entire country except for Veracruz, Mexico City and Acapulco. Since at the time that O'Donojú had left Spain, the Cortes was considering greatly expanding the autonomy of the overseas Spanish possessions, O'Donojú proposed to negotiate a treaty with Iturbide on the terms of the Plan of Iguala.
Sources: en.wikipedia.org
Semax is a synthetic seven-amino-acid peptide derived from a fragment of corticotropin. It is used in Russia as a nasal preparation, while elsewhere it is studied as a research compound. It is not approved as a medicine in most countries.
Its sequence corresponds to the 4-10 region of corticotropin extended by three residues. This fragment lacks the region responsible for adrenal steroid release, so it is explored for neural rather than hormonal effects. The relationship explains the compound's classification among ACTH-derived peptides.
It holds approval in Russia for several neurological indications as a nasal spray or drop formulation. Regulatory agencies in the United States and the European Union have not approved it. Products sold elsewhere are generally labeled for research use only.
The main proposal is modulation of neurotrophic factors such as brain-derived neurotrophic factor, supported largely by animal experiments. Receptor-level targets have not been firmly established. Most reviews describe the mechanism as only partially characterized.