neurogenesis

ISX-9 (Isoxazole 9) is essential for activating neuron-specific genes and serves as a neurogenesis inducer.

TTK21 is an activator of CBP p300 histone acetyltransferase activity.

Moclobemide (Ro111163) is a reversible inhibitor of monoamine oxidase type A; (RIMA); (see MONOAMINE OXIDASE INHIBITORS) that has antidepressive properties.

Compound 3, known as 5-LOX MAOs-IN-1, acts as an inhibitor of 5-LOX MAOs and is an effective free radical scavenger, displaying antioxidant characteristics. It has demonstrated neuroprotective effects in cell models damaged by oxidative stress and is capable of activating the neurogenesis microenvironment in adult mouse neural stem cells. This compound is utilized in research focused on neurodegenerative diseases.

BNN-20 is a synthetic micro-neurotrophic factor that mimics Brain-Derived Neurotrophic Factor (BDNF) and exhibits region-specific neuroprotective and neurogenesis-promoting effects. It is applicable in research related to Parkinson's disease.

4-PivO-NMT chloride is an indole derivative-based regulator of the AMPK signaling pathway. It modulates neurogenesis or neurite outgrowth by influencing AMPK activity and holds potential for research in neurological disorders, pain, and inflammation.

ASM-IN-3 (Compound 21b) is a selective acid sphingomyelinase (ASM) inhibitor that can penetrate the blood-brain barrier, with an IC50 of 3.37 μM against purified human ASM. By inhibiting ASM activity in the hippocampus and promoting neurogenesis, ASM-IN-3 alleviates depressive-like behavior in reserpine-induced depressive rats.

GSK-3β inhibitor24 (Compound 41) is a potent GSK-3β inhibitor with an IC50 of 0.22 nM. It increases GSK-3β phosphorylation at the Ser9 site in a dose-dependent manner and inhibits tau protein hyperphosphorylation by reducing the abundance of p-tau-Ser396. The compound upregulates β-catenin and neurogenesis-related markers (GAP43 and MAP-2), demonstrating significant anti-Alzheimer's disease (AD) activity.

GSK3β-IN-2 (Compound S01) is an inhibitor of GSK3β with an IC50 of 0.35 nM. It activates the Wnt β-catenin signaling pathway, promoting neurogenesis and neurite outgrowth. GSK3β-IN-2 reduces tau protein phosphorylation induced by Aβ at the Ser396 site, thereby decreasing neurofibrillary tangles. Furthermore, GSK3β-IN-2 improves Alzheimer's disease symptoms in a zebrafish model.

Notch signaling pathway activator; enhances the self-renewal capability of neural stem cells (NSCs) via Notch signaling pathway activation in vitro and in vivo. Promotes the expression of Notch target genes, Hes3 and Hes5. Expands the NSCs pool and promotes endogenous neurogenesis in the hippocampal dentate gyrus (DG) after chronic administration in mice. Increases the spatial and episodic memory in mice.

Ganglioside GD3 is synthesized by the addition of two sialic acid residues to lactosylceramide and can serve as a precursor to the formation of more complex gangliosides by the action of glycosyl- and sialyltransferases. It induces apoptosis in HuT-78 cutaneous T cell lymphoma cells in a concentration-dependent manner and disrupts the mitochondrial membrane potential when used at a concentration of 200 μM. Expression of ganglioside GD3 in GD3-negative SK-MEL-28-N1 malignant melanoma cells increases both cell proliferation and invasion in vitro. Ganglioside GD3-deficient adult mice exhibit progressive loss of the neural stem cell (NSC) pool and impaired neurogenesis. Ganglioside GD3 mixture contains ganglioside GD3 molecular species with C18:1 and C20:1 sphingoid backbones.

Betamethasone 21-phosphate is a synthetic glucocorticoid.1It prevents increases in macrophage and eosinophil numbers in bronchoalveolar lavage fluid (BALF) and decreases in blood leukocyte numbers in a guinea pig model of parainfluenza-3 viral infection when administered at a dose of 8 mg/kg but does not prevent airway hyperresponsiveness after infection.2Betamethasone 21-phosphate inhibits cell infiltration into the aqueous humor in a rat model of endotoxin-induced uveitis when administered topically or subcutaneously at doses of 0.01-1% or 1 mg/kg, respectively.3It increases maximal lung pressure volume curves in fetal sheep when administered to pregnant ewes at 0.75 gestation at doses of 80 and 170 μg/kg.1Betamethasone 21-phosphate increases body weight, impairs learning and memory, increases anxiolytic behavior, and reduces hippocampal neurogenesis in CD-1 mice but reduces body weight and increases neurogenesis with no effect on anxiety in high-anxiety DBA/2 mice when administered at a dose of approximately 25 mg/kg per day in the drinking water for seven weeks.4Formulations containing betamethasone 12-phosphate and betamethasone acetate have been used in the treatment of severe allergic conditions and a variety of immune-related conditions. 1.Loehle, M., Schwab, M., Kadner, S., et al.Dose-response effects of betamethasone on maturation of the fetal sheep lungAm. J. Obstet. Gynecol.202(2)186.e181-186.e187(2010) 2.Leusink-Muis, A., Ten Broeke, R., Folkerts, G., et al.Betamethasone prevents virus-induced airway inflammation but not airway hyperresponsiveness in guinea pigsClin. Exp. Allergy29(Suppl. 2)82-85(1999) 3.Tsuji, F., Sawa, K., Kato, M., et al.The effects of betamethasone derivatives on endotoxin-induced uveitis in ratExp. Eye Res.64(1)31-36(1997) 4.Aiello, R., Crupi, R., Leo, A., et al.Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesisBehav. Brain Res.278155-166(2015)

Nrf2-ARE hMAO-B QR2 modulator 1, a resveratrol derivative and multi-target-directed ligand (mtdl), activated the NRF2-ARE pathway (CD = 9.83 μM), selectively inhibited hMAO-B and QR2（quinone reductase-2，NQO2) (IC 50 = 8.05 and 0.57 μM), and was able to promote hippocampal neurogenesis and exert neuroprotective and antioxidant effects in an Alzheimer's disease model.

Yhhu-3792 activates Notch signaling pathway and promotes the expression of Hes3 and Hes5. Yhhu-3792 enhanced the self-renewal ability of neural stem cells (NSCs), expanded the NSC pool and promoted endogenous neurogenesis in the dentate gyrus (DG) of the hippocampus in mice. Yhhu-3792 can improve the situational and spatial memory ability of mice. Yhhu-3792 has research potential in DG dysfunction related to memory impairment.

Yonkenafil (Tunodafil), a novel phosphodiesterase 5 (PDE5) inhibitor, effectively reduces cerebral infarction, neurological deficits, edema, and neuronal damage in the infarcted area, potentially enhancing cognitive function through neurogenesis modulation and offering therapeutic effects on Alzheimer's disease.

ER272 is a natural PKC activator, inducing hippocampal neurogenesis.

Spadin TFA, a natural peptide originating from a propeptide in blood, acts as a powerful TREK-1 channel inhibitor with an IC 50 of 10 nM. It boosts dorsal raphe nucleus 5-HT neurotransmission in mice, activates hippocampal CREB, and promotes neurogenesis. This compound is useful for antidepressant research [1] [2].

MR 409, a selective growth hormone-releasing hormone (GHRH) agonist, exhibits notable neuroprotective properties by augmenting endogenous neurogenesis in cerebral ischemic mice and demonstrates the ability to inhibit in vivo lung cancer growth [1] [2] [3] [4].

Yhhu-3792 hydrochloride is a compound that bolsters the self-renewal capacity of neural stem cells (NSCs), catalyzes the Notch signaling pathway, and upregulates expression of Hes3 and Hes5. It augments the NSC pool, stimulates endogenous neurogenesis in the mouse hippocampal dentate gyrus (DG), and enhances mice's spatial and episodic memory skills. This compound shows promise for researching learning and memory impairments linked to DG dysfunction [1].

Compound 4h, also known as 5-HT7R antagonist 2, is a selective inhibitor of the 5-HT7R that disrupts both G protein and β-arrestin signaling pathways. It exhibits a K_i value of 67 nM, with IC_50 values of 2.59 μM in cAMP assays and 39.57 μM in Tango tests. This antagonist is noted for its potential to mitigate repetitive behaviors associated with autism spectrum disorder (ASD) and to foster the restoration of neurogenesis impaired by ASD [1]. Pharmacokinetic analysis in ICR male mice following intravenous and intraperitoneal administration shows a T_max of 0.08 hours and 0.25 hours, a T_1 2 of 0.77 hours and 1.06 hours, and a C_max of 33.07 ng mL and 156.44 ng mL, respectively. The AUC_last was recorded at 28.31 ng·h mL and 143.27 ng·h mL, with a clearance rate (CL) of 41.61 L h kg for intravenous administration. The volume of distribution at steady state (V_ss) was 32.43 L kg, the mean residence time (MRT) was 0.79 hours and 0.93 hours, and the bioavailability (F) was calculated at 50.60% [1].

2-Methoxystypandrone displays an immunomodulatory effect in a cellular model, it blocks inflammatory responses by impairing NF-κB signaling to limit the inflammation and oxidative stress for preservation of BBB integrity. 2-Methoxystypandrone concomitant