References

Lelieveldt L (2019) Chemical strategies for antigen-selective targeting of autoreactive B Cells. Chapter 2: Sequential prodrug strategy to target and eliminate ACPA-selective autoreactive B cells. Radboud Universiteit Nijmegen Nijmegen, Netherlands 45-64. Thesis.

Objective: To develop a method to target and selectively eliminate autoreactive B cells that produce anti-citrullinated proteins antibodies (ACPA) using a sequential antigen prodrug targeting strategy, as a treatment for Rheumatoid Arthritis (RA).

Summary: The study used a synthesized cyclic citrullinated peptide (CCP) antigen suitable for BCR binding and demonstrated that binding by ACPA was impaired upon introduction of a carboxy-pnitrobenzyl (CNBz) caging group at the side chain of the citrulline residue. Enzymatic reduction of the CNBz moiety by nitroreductase fully restored citrulline-selective recognition by both ACPA and ACPA-expressing B cells and showed targeted cell death of CCP-recognizing B cells only. These results mark an important step towards antigen-selective B cell targeting in general and more specifically in RA.

Usage: Streptavidin-ZAP mixed with biotinylated CCP peptides was tested in cytotoxicity assays. The exposure of cells to CCP-SA-ZAP at 1 nM as well as the activated CCP(CNBz) induced death of up to 60% of ACPA-expressing B cells.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Fatima M, Ren X, Pan H, Slade HFE, Asmar AJ, Xiong CM, Shi A, Xiong AE, Wang L, Duan B (2019) Spinal somatostatin-positive interneurons transmit chemical itch. Pain 160(5):1166-1174. doi: 10.1097/j.pain.0000000000001499

Objective: To further study the cellular identity of spinal interneurons that contribute to itch processing.

Summary: Findings reveal a novel spinal mechanism for sensory encoding of itch perception.

Usage: Npra receptor–expressing spinal cord interneurons were ablated through intrathecal injection of Nppb-SAP (5 μg/10 μL) or control Blank-SAP in lumbar segment 3 to 4. Behavioral analyses were performed 1 week after the toxin injection.

Related Products: Nppb-SAP (Cat. #IT-69), Blank-SAP (Cat. #IT-21)

Chun E, Bumanglag AV, Burke SN, Sloviter RS (2019) Targeted hippocampal GABA neuron ablation by stable substance P-saporin causes hippocampal sclerosis and chronic epilepsy in rats. Epilepsia 60(5):e52-e57. doi: 10.1111/epi.14723

Objective: Hippocampal GABA neurons were targeted for selective elimination to determine whether a focal hippocampal GABAergic defect in an otherwise normal brain can initiate cryptogenic temporal lobe epilepsy with hippocampal sclerosis.

Summary: Hippocampal GABAergic dysfunction is epileptogenic and can produce the defining features of cryptogenic temporal lobe epilepsy.

Usage: Intrahippocampal injections of SSP-SAP (0.4 ng/10 nL) were performed using a 0.5-μL Neuros Syringe lowered into four hippocampal sites along both the transverse and longitudinal hippocampal axes bilaterally.

Related Products: SSP-SAP (Cat. #IT-11)

Read the featured article in Targeting Trends.

Alarautalahti V, Ragauskas S, Hakkarainen JJ, Uusitalo-Järvinen H, Uusitalo H, Hyttinen J, Kalesnykas G, Nymark S (2019) Viability of mouse retinal explant cultures assessed by preservation of functionality and morphology. Invest Ophthalmol Vis Sci 60(6):1914-1927. doi: 10.1167/iovs.18-25156 PMID: 31042799

Summary: Organotypic retinal explant cultures have been used to study retinal development, retinal diseases and injuries, drug screening, and retinal stem cell therapies.

Usage: The amount of ganglion cells and melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs) were detected by staining of RNA-binding protein. Melanopsin detection by immunostaining. 1:2500

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

Porter D, Moore A, Goodman R, Hileman S, Coolen L, Lehman M (2019) Cell-specific ablation of GnRH neurons using kisspeptin-saporin in the preoptic area of sheep, but not mice. J Endocrine Society 3(1):SAT–421. ENDO 2019 – 101st Annual Meeting of the Endocrine Society, New Orleans, Louisiana doi: 10.1210/js.2019-SAT-421

Objective: To invesigate the potential of integrin α10β1 as a therapeutic target in glioblastomas (GBMs).

Summary: Integrin α10β1 has a crucial role in the migration, proliferation, and survival of GBM cells and that an integrin α10β1 antibody–drug conjugate induced cell death of GBM cells both in vitro and in vivo.

Usage: Infusions of anti-10-SAP or Anti-ctrl-SAP were made icv (1 µg/2 L per infusion).

Related Products: Custom Conjugates

Kim E, Hwang S-H, Kim H-K, Abdi S, Kim HK (2019) Losartan, an angiotensin II type 1 receptor antagonist, alleviates mechanical hyperalgesia in a rat model of chemotherapy-induced neuropathic pain by inhibiting inflammatory cytokines in the dorsal root ganglia. Mol Neurobiol 56(11):7408-7419. doi: 10.1007/s12035-019-1616-0 PMID: 31037647

Objective: To assess losartan’s analgesic effect on paclitaxel-induced neuropathic pain (PINP) in rats and its mechanism of action in dorsal root ganglion (DRG).

Summary: The mechanical thresholds, protein levels of inflammatory cytokines, and cellular location of AT1R and interleukin 1β (IL-1β) in the DRG were assessed with behavioral testing, Western blotting, and immunohistochemistry, respectively.

Usage: western blot (1:100)

Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)

Thorén MM, Chmielarska Masoumi K, Krona C, Huang X, Kundu S, Schmidt L, Forsberg-Nilsson K, Floyd Keep M, Englund E, Nelander S, Holmqvist B, Lundgren-Åkerlund E (2019) Integrin α10, a novel therapeutic target in glioblastoma, regulates cell migration, proliferation, and survival. Cancers (Basel) 11(4):587. doi: 10.3390/cancers11040587 PMID: 31027305

Objective: To investigate the potential of integrin alpha10beta1 as a therapeutic target in glioblastomas (GBMs).

Summary: Integrin alpha10beta1 has a crucial role in the migration, proliferation, and survival of GBM cells and that an integrin alpha10beta1 antibody–drug conjugate induced cell death of GBM cells both in vitro and in vivo.

Usage: Infusions of anti- 10-SAP or Anti-ctrl-SAP were made icv (1 mcg/2 L per infusion).

Related Products: Custom Conjugates

Pang HW, Linares A, Couling L, Santollo J, Ancheta L, Daniels D, Speth RC (2019) Novel high molecular weight albumin-conjugated angiotensin II activates β-arrestin and G-protein pathways. Endocrine 66(2):349-359. doi: 10.1007/s12020-019-01930-z

Objective: To study the ability of a novel bovine serum albumin-angiotensin II (BSA-Ang II) conjugate to effect responses of the AT1 angiotensin II receptor subtype mediated by the G-protein-coupled and the beta-arrestin pathways.

Summary: BSA-Ang II and Ang II stimulated water appetite equivalently but BSA-Ang II stimulated saline appetite more than Ang II. Both BSA-Ang II and Ang II were considerably more potent at causing calcium mobilization than β-arrestin binding.

Usage: Angiotensin II (Ang II) was conjugated with bovine serum albumin and compared with Ang II for competition binding to AT1 receptors, to stimulate aldosterone release from adrenocortical cells, to promote beta-arrestin binding to AT1 receptors, to promote calcium mobilization, and stimulate drinking of water and saline by rats.

Related Products: Custom Conjugates

Suarez AN, Noble EE, Kanoski SE (2019) Regulation of memory function by feeding-relevant biological systems: Following the breadcrumbs to the hippocampus. Front Mol Neurosci 12:101. doi: 10.3389/fnmol.2019.00101 PMID: 31057368

Objective: To review the literature describing interconnections between the memory and feeding circuits of the body.

Summary: Gastrointestinal and memory systems within the body are heavily intertwined, something that has been evolutionarily selected for by having to remember food locations, social factors, etc. CCK-SAP (IT-31) has been used to study the connection of gastrointestinal-derived vagal-sensory neurons by selectively lesioning them. These CCK-SAP-treated rats were compared to un-lesioned animals and showed reduced brain-derived neurotrophic factor and memory impairment

Related Products: CCK-SAP (Cat. #IT-31)

See Also:

• Suarez AN et al. Gut vagal sensory signaling regulates hippocampus function through multi-order pathways. Nat Commun 9(1):2181, 2018.

Deura C, Minabe S, Ikegami K, Inoue N, Uenoyama Y, Maeda KI, Tsukamura H (2019) Morphological analysis for neuronal pathway from the hindbrain ependymocytes to the hypothalamic kisspeptin neurons. J Reprod Dev 65(2):129-137. doi: 10.1262/jrd.2018-122

Objective: To examine the existence of a neuronal pathway from the hindbrain ependymocytes to kisspeptin neurons in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV).

Summary: The hindbrain ependymocytes have neuronal connections with the kisspeptin neurons, most probably via hindbrain noradrenergic and CRH neurons to relay low energetic signals for regulation of reproduction.

See: I’Anson H et al. Immunotoxic destruction of distinct catecholaminergic neuron populations disrupts the reproductive response to glucoprivation in female rats. Endocrinology 144(10):4325-4331, 2003.

Related Products: Anti-DBH-SAP (Cat. #IT-03)