targeted-toxins

Leanza G, Zorec R (2023) Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease. Function (Oxf) 4(1):zqac060., IT. doi: 10.1093/function/zqac060 PMID: 36590326

Summary: These results indicate a prominent role of NA-neurons vs. ACh neurons in impairments of working memory, relevant for AD, and are consistent with an astrocyte-specific metabolic impairment in a mouse model of intellectual disability.

Usage: Bilateral icv injection of 192-IgG-SAP and/or Anti-DBH-SAP

Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)

Lee W, Song G, Bae H (2022) Laminarin attenuates ros-mediated cell migration and invasiveness through mitochondrial dysfunction in pancreatic cancer cells. Antioxidants (Basel) 11(9):1714. doi: 10.3390/antiox11091714

Objective: To determine the effects of laminarin on pancreatic cancer.

Summary: Laminarin showed synergistic effects when combined with 5-FU, a standard anticancer agent for pancreatic ductal adenocarcinoma (PDAC) with potential as a treatment for PDAC.

Usage: Lund et al. work on 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin Anti-CD105-SAP.

Related Products: Anti-CD105-SAP (Cat. #IT-80)

See Also:

• Lund K et al. 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin CD105-saporin. J Exp Clin Cancer Res 36(1):185, 2017.

Madrid LI, Bandhavkar S, Hafey K, Jimenez-Martin J, Milne M, Coulson EJ, Jhaveri DJ (2022) Stimulation of the muscarinic receptor M4 activates quiescent neural precursor cells and ameliorates medial septum cholinergic lesion-induced impairments in adult hippocampal neurogenesis. bioRxiv 2022.08.25.505357. doi: 10.1101/2022.08.25.505357

Objective: To investigate the contribution of basal forebrain medial septum (MS) and diagonal band of Broca (DBB) cholinergic neurons that innervate the hippocampus and the identity of the cholinergic receptor(s) that regulate the production and maturation of new neurons.

Summary: This work reveals stage-specific roles of cholinergic signaling in regulating functionally relevant adult hippocampal neurogenesis.

Usage: Medial septum cholinergic lesion was achieved by infusion of mu p75-SAP (0.4 µg/µl). Rabbit IgG-SAP (0.4 µg/µl) was used as control.

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)

Imado E, Sun S, Abawa AR, Tahara T, Kochi T, Huynh TNB, Asano S, Hasebe S, Nakamura Y, Hisaoka-Nakashima K, Kotake Y, Irifune M, Tsuga K, Takuma K, Morioka N, Kiguchi N, Ago Y (2022) Prenatal exposure to valproic acid causes allodynia associated with spinal microglial activation. Neurochem Int 160:105415. doi: 10.1016/j.neuint.2022.105415

Objective: To further understand the mechanism underlying sensory phenotypes in autism spectrum disorder (ASD).

Summary: The authors investigated the age-dependent tactile sensitivity in an animal model of ASD induced by prenatal exposure to valproic acid and subsequently assessed the involvement of microglia in the spinal cord in pain processing.

Usage: To deplete microglia in the spinal cord, Mac-1-SAP (11.2 μg/5.5 μl) was injected intrathecally at the level of L4–L5 in adult (8-week-old) mice.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Orciani C, Hall H, Pentz R, Foret MK, Do Carmo S, Cuello AC (2022) Long-term nucleus basalis cholinergic depletion induces attentional deficits and impacts cortical neurons and BDNF levels without affecting the NGF synthesis. J Neurochem doi: 10.1111/jnc.15683

Objective: To determine whether reciprocal interaction of basal forebrain cholinergic neurons (BFCN) impact neurotrophin availability and affect cortical neuronal markers.

Summary: There is a neuroprotective role of cholinergic neurotransmission in the adult, fully-differentiated cortex.

Usage: Immunolesioned BFCN projecting mainly to the cortex with 192-IgG-SAP (bilateral 0.5 ug/ul; 1.0 ul/hemisphere) in 2.5 month-old Wistar rats.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Akmese C, Sevinc C, Halim S, Unal G (2022) Differential role of GABAergic and cholinergic ventral pallidal neurons in behavioral despair, conditioned fear memory and active coping. bioRxiv 2022.07.21.500949. doi: 10.1101/2022.07.21.500949

Related Products: 192-IgG-SAP (Cat. #IT-01), GAT1-SAP (Cat. #IT-32)

Grady FS, Boes AD, Geerling JC (2022) A century searching for the neurons necessary for wakefulness. Front Neurosci 16:930514. doi: 10.3389/fnins.2022.930514

Objective: This review article attempts to summarize research that has investigated the neurons necessary for wakefulness.

Summary: The authors summarize animal experiments and research performed in different brain regions to further understand wakefulness. Several saporin conjugates are discussed.

Usage: Lesions of the basal forebrain were done by injecting a 0.1% solution of either 192-IgG-SAP or Orexin-SAP at four different sites (Fuller et al. and Geraschenko et al.); Intraventricular injection of Anti-DBH-SAP (Gompf et al.); Bilateral injections of 192-IgG-SAP (Kaur et al.).

Related Products: Orexin-B-SAP (Cat. #IT-20)

See Also:

• Fuller P et al. Reassessment of the structural basis of the ascending arousal system. J Comp Neurol 519(5):933-956, 2011.
• Gerashchenko D et al. Insomnia following hypocretin2-saporin lesions of the substantia nigra. Neuroscience 137(1):29-36, 2006.
• Gompf HS et al. Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment. J Neurosci 30(43):14543-14551, 2010.
• Kaur S et al. Effects of ibotenate and 192IgG-saporin lesions of the nucleus basalis magnocellularis/substantia innominata on spontaneous sleep and wake states and on recovery sleep after sleep deprivation in rats. J Neurosci 28:491-504, 2008.

Q: What are neuropeptide-toxins and how do they work?

A: Neuropeptide-toxin conjugates are made up of the ribosome-inactivating protein, saporin, coupled to a naturally-occurring or synthetically-modified neuropeptide such as Substance P or dermorphin. The conjugate has binding specificity similar to the native, unconjugated neuropeptide. When the neuropeptide binds to its cognate receptor, the conjugate is internalized. Once inside the target cell within an endosome, the neuropeptide and saporin separate and some of the saporin translocates into the cytoplasm where it catalytically inactivates ribosomes resulting in cell death.

Q: Are neuropeptide-toxins effective suicide transport agents?

A: The general answer to this question is not currently known. However, in the instance of intrathecally injected dermorphin-SAP (Cat. #IT-12), the evidence does NOT favor suicide transport of the neuropeptide-toxin conjugate. When supramaximal doses of dermorphin-SAP (750 ng) are injected into the lumbar subarachnoid space of adult rats, less than 1% of lumbar dorsal root ganglion cells show evidence of saporin activity. This is in spite of the fact that many of these neurons express the targeted mu opioid receptor on their central terminals in the superficial dorsal horn of the spinal cord. This assertion is based on analysis of over 16,000 neurons from dorsal root ganglia in six rats.

See: Targeted Toxins

Griffin JM, Healy FM, Dahal LN, Floisand Y, Woolley JF (2022) Worked to the bone: antibody-based conditioning as the future of transplant biology. J Hematol Oncol 15(1):65. doi: 10.1186/s13045-022-01284-6

Objective: To analyze the current status of antibody-based drugs in pre-transplant conditioning regimens and assess their potential in the future of transplant biology.

Summary: This review article suggests that antibody-based conditioning regimens may be the next big advancement in hematopoietic stem cell transplantation.

Related Products: Anti-CD117-SAP (Cat. #IT-83)

See Also:

• Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.
• Castiello MC et al. Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency. J Allergy Clin Immunol 147(1):309-320.e6, 2021.
• Czechowicz A et al. Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation. Nat Commun 10:617, 2019.
• Li Z et al. Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation. Nat Commun 10:616, 2019.

Krieger JP, Asker M, Van der Velden P, Börchers S, Richard JE, Maric I, Longo F, Singh A, De Larigue G, Skibicka KP (2022) Neural pathway for gut feelings: vagal interoceptive feedback from the gastrointestinal tract is a critical modulator of anxiety-like behavior. Biological Psychiatry in press. doi: 10.1016/j.biopsych.2022.04.020

Objective: To determine how the sensing of gastrointestinal state affects anxiety.

Summary: Vagal sensory signals from the gastrointestinal tract are critical for baseline and feeding-induced tuning of anxiety via the central amygdala in rats. The article results suggest vagal gut-brain signaling as a target to normalize interoception in anxiety.

Usage: 1.5 ul of CCK-SAP or Blank-SAP were delivered into each nodose ganglion at 250 ng/ul.

Related Products: CCK-SAP (Cat. #IT-31), Blank-SAP (Cat. #IT-21)

Chen LQ, Lv XJ, Guo QH, Lv SS, Lv N, Yu J, Xu WD, Zhang YQ (2022) Asymmetric activation of microglia in the hippocampus drives anxiodepressive consequences of trigeminal neuralgia. bioRxiv 2022.04.16.488241. doi: 10.1101/2022.04.16.488241

Related Products: Mac-1-SAP rat (Cat. #IT-33)

Mueller M, Thompson R, Osman KL, Andel E, DeJonge CA, Kington S, Stephenson Z, Hamad A, Bunyak F, Nichols NL, Lever TE (2022) Impact of limb phenotype on tongue denervation atrophy, dysphagia penetrance, and survival time in a mouse model of ALS. Dysphagia doi: 10.1007/s00455-022-10442-4

Related Products: CTB-SAP (Cat. #IT-14)

See Also:

• Lind LA et al. Tongue and hypoglossal morphology after intralingual cholera toxin B-saporin injection. Muscle Nerve 63(3):413-420, 2021.

Marcucci F, Lappi DA, Ghislieri M, Martineau D, Siena S, Bregni M, Soria M, Gianni AM (1989) In vivo effects in mice of an anti-T cell immunotoxin. J Immunol 142:2955-2960.

Related Products: OX7-SAP (Cat. #IT-02)

Liu W, Li J, Yang M, Ke X, Dai Y, Lin H, Wang S, Chen L, Tao J (2022) Chemical genetic activation of the cholinergic basal forebrain hippocampal circuit rescues memory loss in Alzheimer’s disease. Alzheimers Res Ther 14(1):53. doi: 10.1186/s13195-022-00994-w

Related Products: 192-IgG-SAP (Cat. #IT-01)

See Also:

• Tomaszewicz M et al. Changes in cortical acetyl-CoA metabolism after selective basal forebrain cholinergic degeneration by 192IgG-saporin. J Neurochem 87(2):318-324, 2003.

Nguyen KL, Lamerand SR, Deshpande RP, Taylor BK (2021) Featured Article: Selective ablation of IB4+ primary afferent neurons reduces mechanical and cold hyperalgesia in an EAE mouse model of multiple sclerosis. Targeting Trends 22

Related Products: IB4-SAP (Cat. #IT-10), Blank-SAP (Cat. #IT-21)

Read the featured article in Targeting Trends.

See Also:

• Nguyen KL et al. Contribution of small diameter non-peptidergic primary afferent neurons to central neuropathic pain in a new, more clinically relevant mouse model of multiple sclerosis. Neuroscience 2021 Abstracts P377/07, 2021. Society for Neuroscience, Virtual

Charlesworth CT, Hsu I, Wilkinson AC, Nakauchi H (2022) Immunological barriers to haematopoietic stem cell gene therapy. Nat Rev Immunol 1-15. doi: 10.1038/s41577-022-00698-0

Objective: This review article attempts to encourage more research to address the immunological barriers to haematopoietic stem cell based gene therapies.

Summary: The authors lay out the history and clinical trials of hematopoietic stem cell gene therapy and then discuss the challenges of both innate immunity and adaptive immunity.

Usage: This review mentions a publication that used Anti-CD117-SAP to ablate hematopoietic stem cells.

Related Products: Anti-CD117-SAP (Cat. #IT-83)

See Also:

• Czechowicz A et al. Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation. Nat Commun 10:617, 2019.

Yun-Fei L, Zhang J, Wang XQ, Peng JJ, Ling BF, Liu FT, Yang F, Dong G, Yu YQ (2022) Noradrenergic innervations of the medial prefrontal cortex mediate empathy for pain in rats via the α1 and β receptors. Behav Brain Res 10:113828. doi: 10.1016/j.bbr.2022.113828

Objective: To study the roles of the locus coeruleus (LC) to medial prefrontal cortex (mPFC) pathway in pain empathy in rats.

Summary: Results indicate that noradrenergic innervations in the mPFC mediate empathy for pain in rats via the α1 and β receptors.

Usage: Noradrenergic innervations of the mPFC were selectively eliminated through intra-mPFC injections of Anti-DBH-SAP.

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

Ancheta LR, Shramm PA, Bouajram R, Higgins D, Lappi DA (2022) Saporin as a commercial reagent: its uses and unexpected impacts in the biological sciences-tools from the plant kingdom. Toxins (Basel) 14(3):184. doi: 10.3390/toxins14030184

Read complete article.

Xu L, Füredi N, Lutter C, Geenen B, Pétervári E, Balaskó M, Dénes Á, Kovács KJ, Gaszner B, Kozicz T (2022) Leptin coordinates efferent sympathetic outflow to the white adipose tissue through the midbrain centrally-projecting Edinger-Westphal nucleus in male rats. Neuropharmacology 205:108898. doi: 10.1016/j.neuropharm.2021.108898

Objective: To show that leptin bound to neurons of the Edinger-Westphal nucleus (EWcp) stimulated STAT3 phosphorylation and increases urocortin 1 (Ucn1)-production in a time-dependent manner.

Summary: EWcp/LepRb/Ucn1 neurons respond to leptin signaling as well as control white adipose tissue size and fat metabolism without altering food intake.

Usage: Ablation of EWcp leptin receptor (LepRb) positive neurons with leptin-saporin. Either unconjugated saporin (53 ng in 80 nl MQ, or Leptin-SAP (90 ng in 80 nl MQ, was injected into the rat midbrain.

Related Products: Leptin-SAP (Cat. #IT-47), Saporin (Cat. #PR-01)

Ujvári B, Pytel B, Márton Z, Bognár M, Kovács LÁ, Farkas J, Gaszner T, Berta G, Kecskés A, Kormos V, Farkas B, Füredi N, Gaszner B (2022) Neurodegeneration in the centrally-projecting Edinger-Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat. J Neuroinflammation 19(1):31. doi: 10.1186/s12974-022-02399-w

Objective: To investigate whether neuron loss and alpha-synuclein accumulation in the urocortin 1 containing (UCN1) cells of the centrally-projecting Edinger-Westphal (EWcp) nucleus is associated with anxiety and depression-like state in the rat.

Summary: Neurodegeneration of urocortinergic EWcp contributes to the mood-related non-motor symptoms in toxic models of Parkinson’s disease in the rat.

Usage: Leptin-SAP or unconjugated Saporin (0.08 μl) was injected into the EWcp area. This selective ablation of UCN1 neurons was used to validate the depression-like phenotype in rats. Behavioral, functional–morphological, biochemical and histopathological tools were used to test the motor coordination, mood status as well as morphological changes in the brain.

Related Products: Saporin (Cat. #PR-01), Leptin-SAP (Cat. #IT-47)