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2019 Targeting Trends Review
Knockdown of fidgetin improves regeneration of injured axons by a microtubule-based mechanism.
Matamoros AJ, Tom VJ, Wu D, Rao Y, Sharp DJ, Baas PW (2019) Knockdown of fidgetin improves regeneration of injured axons by a microtubule-based mechanism. J Neurosci 39(11):2011-2024. doi: 10.1523/JNEUROSCI.1888-18.2018 PMID: 30647150
Objective: To test whether fidgetin knockdown assists axonal regeneration.
Summary: Results show that DRG neurons in which fidgetin was knocked down displayed enhanced regeneration of axons across the dorsal root entry zone into the spinal cord. The results establish fidgetin as a novel therapeutic target to augment nerve regeneration.
Usage: immunohistochemistry
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Inhibition of methamphetamine self-administration and reinstatement by central blockade of angiotensin II receptor in rats.
Xu X, Pan J, Li X, Cui Y, Mao Z, Wu B, Xu H, Zhou W, Liu Y (2019) Inhibition of methamphetamine self-administration and reinstatement by central blockade of angiotensin II receptor in rats. J Pharmacol Exp Ther 369(2):244-258. doi: 10.1124/jpet.118.255729 PMID: 30867225
Objective: To explore the role of central angiotensin II receptor (ATR) in drug taking and seeking behavior associated with methamphetamine (METH) use disorder.
Summary: The AT1R-PLCβ-CREB signaling pathway was found to be associated with the effect of AT1R on the drug-taking and drug-seeking behavior involving METH use disorder.
Usage: Membranes were incubated at 4°C overnight (1:1000). Western blot.
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Serotonin and motherhood: From molecules to mood.
Pawluski JL, Li M, Lonstein JS (2019) Serotonin and motherhood: From molecules to mood. Front Neuroendocrinol 53:100742. doi: 10.1016/j.yfrne.2019.03.001
Summary: Serotonin may affect how mothers perceive or behaviorally readjust to changes in the sensory cues emitted by their offspring as they age. The DR serotonin-lesioned mothers studied by Holschbach and colleagues (2018) were much less maternally aggressive, which was concomitant with reduced serotonin-immunoreactive fiber density in the anterior hypothalamus, a brain site previously implicated in serotonin’s influence on aggressive behaviors in male animals.
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Cholinergic deficit induced by central administration of 192IgG-Saporin is associated with activation of microglia and cell loss in the dorsal hippocampus of rats
Dobryakova YV, Volobueva MN, Manolova AO, Medvedeva TM, Kvichansky AA, Gulyaeva NV, Markevich VA, Stepanichev MY, Bolshakov AP (2019) Cholinergic deficit induced by central administration of 192IgG-Saporin is associated with activation of microglia and cell loss in the dorsal hippocampus of rats. Front Neurosci 13:146. doi: 10.3389/fnins.2019.00146
Objective: To study the histopathology of the hippocampus and the responses of microglia and astrocytes using immunohistochemistry and neuroglial gene expression.
Summary: Cholinergic degeneration in the medial septal area induced by intracerebroventricular administration of 192IgG-saporin results in an increase in the number of microglial cells and neuron degeneration in the dorsal hippocampus.
Usage: 192-IgG-SAP was injected bilaterally into both ventricles (i.c.v.) at a dose of 4 μg/site.
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Spinal α2-adrenoceptors and neuropathic pain modulation; therapeutic target.
Bahari Z, Meftahi GH (2019) Spinal α2-adrenoceptors and neuropathic pain modulation; therapeutic target. Br J Pharmacol 176(14):2366-2381. doi: 10.1111/bph.14580
Objective: To provide an an overview of the cellular mechanisms through which brainstem adrenergic descending inhibitory processing can alter spinal pain transmission to the higher centres, and how these pathways change in neuropathic pain conditions focusing on the role of spinal α2‐adrenoceptors in the spinal dorsal horn.
Summary: The α2‐adrenoceptor agonist may be useful to treat neuropathic pain.
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Palladium based nanoparticles for the treatment of advanced melanoma.
Elsey J, Bubley JA, Zhu L, Rao S, Sasaki M, Pollack BP, Yang L, Arbiser JL (2019) Palladium based nanoparticles for the treatment of advanced melanoma. Sci Rep 9:3255. doi: 10.1038/s41598-019-40258-6 PMID: 30824801
Usage: immunohistochemistry (1:300)
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Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model.
Katri A, Dąbrowska A, Löfvall H, Ding M, Karsdal MA, Andreassen KV, Thudium CS, Henriksen K (2019) Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model. Arthritis Res Ther 21(1):68. doi: 10.1186/s13075-019-1819-9 PMID: 30795801
Objective: To investigate if combining a standard of care NSAID (naproxen) with a Key Bioscience peptides (KBP) resulted in improvement in pain scores, as well as disease activity and structural damage in a rat model of rheumatoid arthritis (RA).
Summary: Combination therapy had improved efficacy over naproxen monotherapy; combination therapy resulted in improved health scores, and reduced mechanical and cold allodynia assessment. Furthermore, protection of articular cartilage structure and preservation of bone structure and bone volume were also observed.
Usage: histology (1:4000)
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Degeneration of ipRGCs in mouse models of huntington’s disease disrupts non-image-forming behaviors before motor impairment.
Lin M-S, Liao P-Y, Chen H-M, Chang C-P, Chen S-K, Chern Y (2019) Degeneration of ipRGCs in mouse models of huntington’s disease disrupts non-image-forming behaviors before motor impairment. J Neurosci 39(8):1505. doi: 10.1523/JNEUROSCI.0571-18.2018 PMID: 30587542
Summary: Results show that M1 ipRGCs were susceptible to the toxicity caused by mutant Huntingtin. The resultant impairment of M1 ipRGCs contributed to the early degeneration of the ipRGC–SCN pathway and disrupted circadian regulation during HD progression.
Usage: Immunostaining (1:3000)
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Discovery and development of N-[4-(1-Cyclobutylpiperidin-4-yloxy)phenyl]-2-(morpholin-4-yl)acetamide Dihydrochloride (SUVN-G3031): A novel, potent, selective, and orally active histamine H3 receptor inverse agonist with robust wake-promoting activity.
Nirogi R, Shinde A, Mohammed AR, Badange RK, Reballi V, Bandyala TR, Saraf SK, Bojja K, Manchineella S, Achanta PK, Kandukuri KK, Subramanian R, Benade V, Palacharla RC, Jayarajan P, Pandey S, Jasti V (2019) Discovery and development of N-[4-(1-Cyclobutylpiperidin-4-yloxy)phenyl]-2-(morpholin-4-yl)acetamide Dihydrochloride (SUVN-G3031): A novel, potent, selective, and orally active histamine H3 receptor inverse agonist with robust wake-promoting activity. J Med Chem 62(3):1203-1217. doi: 10.1021/acs.jmedchem.8b01280
Objective: To discover and develop a therapeutic for human sleep disorders.
Summary: Histamine H3 Receptor Inverse Agonist demonstrated high receptor occupancy and marked wake promoting effects with decreased REM sleep in Orexin-B-SAP lesioned rats. This study supports its potential therapeutic utility in treating human sleep disorders.
Usage: Injections (490 ng/0.8 μl) were made bilaterally to the lateral hypothalamus.
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Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation.
Li Z, Czechowicz A, Scheck A, Rossi DJ, Murphy PM (2019) Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation. Nat Commun 10:616. doi: 10.1038/s41467-018-08202-w
Objective: To develop a conditioning protocol for fully MHC-mismatched bone marrow allotransplantation in mice involving transient immunosuppression and selective depletion of recipient hematopoietic stem cells.
Summary: CD117-ADC conditioning promotes skin allograft tolerance.
Usage: Biotinylated monoclonal antibodies directed against mouse CD117 were coupled to Streptavidin-ZAP. Each mouse was injected with 1.5 mg/kg of ADC in a total volume of 300 mcl PBS.
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