targeted-toxins

Milanowski J, Pawłowska M, Woźniak A, Szewczyk-Golec K (2025) Summarizing the role of selected adipokines in parkinson’s disease: What is known about leptin, adiponectin, resistin, visfatin, and progranulin in neurodegeneration?. Molecules 30(22):4431. doi: 10.3390/molecules30224431 PMID: 41302488

Objective: To summarize current evidence and identify potential targets for Parkinson’s disease (PD) treatment or as biomarkers of disease progression.

Summary: The improper secretion and function of leptin have been associated with carcinogenesis and obesity and have also been implicated in neurodegeneration and PD. The administration of Leptin-SAP, to eliminate cells that recognize and internalize leptin, thereby inducing cell ablation, resulted in an increase in anhedonia and signs of anxiety in the rats. However, the procedure did not affect the rats’ motor abilities. Injection led to a decrease in EWcp/UCN1 cells, suggesting neurodegeneration.

Related Products: Leptin-SAP (Cat. #IT-47)

See Also:

• Ujvári B et al. 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, 2022.

Yu C, Li M, Shen F, Gao S, Wang J, He C, Wang L, Wu Y, Du Y (2025) Electroacupuncture alleviates cognitive impairments in APP/PS1 mice via gastric vagal afferent-mediated activation of the nucleus tractus solitarius‒locus coeruleus noradrenergic circuit. Chin Med 20(1):188. doi: 10.1186/s13020-025-01230-x PMID: 41233833

Objective: To demonstrate efficacy in ameliorating Alzheimer’s disease (AD)-related cognitive dysfunction through dual peripheral and central anti-infammatory actions using electroacupuncture (EA).

Summary: Transgenic mice were administrated with EA stimulation and cognitive function was assessed via the Morris water maze and novel object recognition tests. EA at ST36 and ST37 attenuated hippocampal synaptic ultrastructural degeneration. The experimental blockade of vagal aferent neurons via CCK-SAP injection into the nodose ganglion abolished the benefits induced by EA, directly implicating GVAF signaling in the improvement of EA-mediated AD.This intervention suppressed proinflammatory cytokines expression (IL-6, IL-1β, TNF-α) and microglial hyperactivation, effectively rescuing cognitive deficits in AD models.

Usage: CCK-SAP was injected into the nodose ganglion.

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

See Also:

• Diepenbroek C et al. Validation and characterization of a novel method for selective vagal deafferentation of the gut. Am J Physiol Gastrointest Liver Physiol 313:G342-G352, 2017.

Spedding M (2025) Does amyotrophic lateral sclerosis (als) have metabolic causes from human evolution?. Cells 14(21):1734. doi: 10.3390/cells14211734 PMID: 41227379

Objective: To evaluate if recent human genetic variants play major roles in Amyotrophic Lateral Sclerosis (ALS), changing metabolism.

Summary: The authors reviewed Cholera Toxin B (CTB) binding as a tool to study GM1 and fucosylated structures, and to cause denervation. Findings suggest CTB may be used as a surrogate marker of GM1. CTB-SAP causes specific motor neuron death, presumably by binding to and downregulating GM1, and possibly other fucosylated targets; powerful evidence linking loss of GM1 to denervation in ALS.

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

See Also:

• Llewellyn-Smith IJ et al. Tracer-toxins: cholera toxin B-saporin as a model. J Neurosci Methods 103(1):83-90, 2000.
• Ciuro M et al. Mitigating the functional deficit after neurotoxic motoneuronal loss by an inhibitor of mitochondrial fission. Int J Mol Sci 25(13):7059, 2024.
• Gulino R et al. Neuromuscular plasticity in a mouse neurotoxic model of spinal motoneuronal loss. Int J Mol Sci 20(6):1500, 2019.
• Lind LA et al. Hypoglossal motor neuron death via intralingual CTB-saporin (CTB-SAP) injections mimic aspects of amyotrophic lateral sclerosis (ALS) related to dysphagia. Neuroscience 390:303-316, 2018.
• Lewis RD et al. Spinal TNF-α receptor 1 is differentially required for phrenic long-term facilitation (pLTF) over the course of motor neuron death in adult rats. Front Physiol 15, 2024.
• Chew C et al. Exercise is neuroprotective on the morphology of somatic motoneurons following the death of neighboring motoneurons via androgen action at the target muscle. Dev Neurobiol 81(1):22-35, 2021.
• Chew C et al. Exercise is neuroprotective on the morphology of somatic motoneurons following the death of neighboring motoneurons via androgen action at the target muscle. Dev Neurobiol 81(1):22-35, 2021.
• Lind LA et al. Tongue and hypoglossal morphology after intralingual cholera toxin B-saporin injection. Muscle Nerve 63(3):413-420, 2021.
• Keilhoz A et al. Tongue exercise ameliorates structural and functional upper airway deficits in a rodent model of hypoglossal motor neuron loss. Front Neurol 15:1441529, 2024.

Doyle S, Doran MM, Cunningham C, Lowry JP (2025) Real-time in vivo monitoring of cholinergic neurotransmission in the mouse brain using a microelectrochemical choline biosensor. Eur J Neurosci 62)9):e70291. doi: 10.1111/ejn.70291 PMID: 41185145

Objective: To refine an established choline oxidase (ChOx) microelectrochemical biosensor to validate its use for long-term recording in the freely moving mouse.

Summary: Systemic administration of donepezil produced a pronounced decrease in current in both the pre-frontal cortex and hippocampus, with scopolamine and amphetamine resulting in signal increases that were not observed in animals with selective saporin lesioning (mu p75-SAP) of the cholinergic basal forebrain. Furthermore, continuous biosensor recording in both regions displayed diurnal oscillations across repetitive light–dark phases. All are consistent with successful monitoring of endogenous changes in cholinergic neurotransmission.

Usage: Two 1-μL icv injections of either sterile PBS (control animals) or mu p75-SAP (IT-16) at a concentration of 0.6 μg/μL were made into the lateral ventricles usinga NanoFil syringe under the control of an infusion pump at a rate of 0.2 nL/min. Following injection, the needle tip was left in place for 8 min to minimize reflux.

Related Products: mu p75-SAP (Cat. #IT-16)

Yelamali AR, Chendamarai E, Ritchey JK, Rettig MP, DiPersio JF, Persaud SP (2025) Streptavidin-drug conjugates streamline optimization of antibody-based hematopoietic stem cell transplant conditioning. Blood ICT 1(3):100012. doi: 10.1016/j.bict.2025.100012 PMID: 41574174

Objective: To develop and validate a modular streptavidin based antibody drug conjugate platform for optimizing antibody mediated hematopoietic stem cell transplant conditioning.

Summary: The authors demonstrate that a streptavidin drug conjugate system enables rapid comparison of antibody payload combinations for hematopoietic stem cell depletion and leukemia targeting. The study builds on prior work using CD45 targeted immunotoxins to achieve effective hematopoietic niche depletion in murine HSCT models.

Usage: This study references earlier conditioning experiments that utilized Streptavidin-ZAP (IT-27) in combination with biotinylated CD45 antibodies to selectively deplete hematopoietic stem cells in murine HSCT models, typically administered as a single intravenous dose of approximately 75 µg per mouse.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD45.2-SAP (Cat. #IT-91)

Leanza MH, Storelli E, D’Arco D, de Leo G, Kleiner G, Arancio L, Capodieci G, Gulino R, Bava A, Leanza G (2025) Cerebellar contributions to spatial learning and memory: Effects of discrete immunotoxic lesions. Int J Mol Sci 26(19):9553. doi: 10.3390/ijms26199553 PMID: 41096819

Objective: To analyze the behavioral and anatomical effects of discrete injections, in different groups of animals, of the same 192 IgG-saporin toxin into the basal forebrain nuclei and/or into the cerebellar vermis and hemispheres.

Summary: Authors administered, 192 IgG-saporin, selectively targeting cholinergic neurons in the basal forebrain and a subpopulation of cerebellar Purkinje cells, to adult rats bilaterally into the basal forebrain nuclei, the cerebellar cortices or both areas combined. The results suggest important functional interactions between the ascending regulatory inputs from the cerebellum and those arising in the basal forebrain nuclei that would act together to modulate the complex sensory–motor and cognitive processes required to control whole body movement in space.

Usage: (i) bilateral intraventricular injection of 192 IgG-saporin (ICV, n = 12); (ii) bilateral injections of 192 IgG-saporin into the basal forebrain nuclei (BF, n = 12); (iii) injections of 192 IgG-saporin into the cerebellar hemispheres and vermis (CBL, n = 12); and (iv) injections of 192 IgG-saporin into both the basal forebrain nuclei and cerebellar hemispheres and vermis (BF/CBL, n = 12).

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

Herrerias A, Oliverio A, Dvorácskó S, Thyagarajan A, Chedester L, Liu J, Cinar R, Iyer MR, Kunos G, Godlewski G (2026) CB1 receptors on a subset of vagal afferent neurons modulate voluntary ethanol intake in mice. Mol Psychiatry 31(1):48-61. doi: 10.1038/s41380-025-03266-9 PMID: 40975751

Objective: To investigate how peripheral CB1 receptors on vagal afferent neurons regulate voluntary ethanol intake and their role in gut-brain signaling underlying alcohol consumption.

Summary: Selective deletion or ablation of CB1R in nodose ganglion neurons abolished the inhibitory effects of peripheral CB1R antagonists on voluntary ethanol intake. The study identifies CB1R on Gpr65⁺ vagal sensory neurons as critical mediators of gut-brain communication regulating alcohol preference and intake.

Usage: Anti-CB1-SAP (IT-104) or Blank-SAP (IT-21) was injected into the proximity of the nodose ganglion at 250 ng/mL to selectively ablate CB1R-expressing vagal afferent neurons

Related Products: Anti-CB1-SAP (Cat. #IT-104), Blank-SAP (Cat. #IT-21)

Kobayashi K, Miyazaki Y, Sakamoto N, Yamamoto M, Nagat N, Murata T (2025) Long-term scratching analysis of mice using machine learning. PNAS Nexus 4(9):pgaf292. doi: 10.1093/pnasnexus/pgaf292 PMID: 41030291

Objective: To objectively quantify mouse scratching behavior across light and dark cycles using automated, long-term machine learning analysis.

Summary: Naïve BALB/c mice exhibited more frequent and persistent scratching during the light period, and DNFB-induced dermatitis caused biphasic, long-lasting scratching even during rest. The study establishes a continuous behavior analysis method that reveals circadian and pathological pruritus features.

Usage: Bombesin-SAP (IT-40) or Blank-SAP (IT-21) was administered intrathecally at 400 ng in 5 μL PBS.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Alampi MM, Kozlíková M, Mariangeli M, Civita S, Delcanale P, Mussini A, Diaspro A, Bianchini P, Weyergang A, Skarpen E, Berg K, Viappiani C, Abbruzzetti S, Selbo PK (2025) Light-enhanced cytotoxicity and intracellular trafficking of the PD-L1-targeting photoimmunoconjugate EITC-atezolizumab. Biomed Pharmacother 191:118550. doi: 10.1016/j.biopha.2025.118550 PMID: 40946581

Objective: To optimize the cytotoxic efficacy of a photoimmunoconjugate of eosin-5-isothiocyanate and atezolizumab (EITC-atezolizumab) in NSCLC cells; To study the uptake and intracellular transport of atezolizumab; and to evaluate EITC-atezolizumab as a candidate for photochemical internalization (PCI) of the ribosome-inactivating protein gelonin.

Summary: This is the first documentation demonstrating that atezolizumab is transported to CD63-positive organelles, thereby enhancing our understanding of its intracellular trafficking. The study also strengthens the concept of Photoimmunotherapy (PIT) and atezolizumab-based targeting of PD-L1+NSCLCs.

Usage: The cytotoxic efficacy of the PD-L1-targeting immunotoxin (Anti-PD-L1-SAP) was strongly enhanced in PD-L1-positive breast cancer cells by photochemical internalization (PCI),a low-dose, Photodynamictherapy (PDT)-based intracellular drug delivery method.

Related Products: Anti-PD-L1-SAP (Cat. #IT-45)

Hor CC (2025) The dual nature of cold: Unraveling the neural circuits for cool sensing and cold allodynia. Univ Michigan Thesis.

Objective: To elucidate the neural mechanisms underlying innocuous cool sensation from the skin to the brain and the spinal circuitry changes that drive cold allodynia under pathological conditions.

Summary: The study identified distinct spinal interneuron populations mediating innocuous cool sensation (Trhr⁺ neurons) and cold allodynia (Tac1⁺/Calb1⁺ neurons). Ablation of these neurons demonstrated their modality-specific contributions, with Trhr⁺ interneurons responsible for cool detection and Tac1⁺/Calb1⁺ neurons for pathological cold hypersensitivity, revealing a spinal circuit basis for temperature discrimination and pain plasticity.

Usage: Bombesin-SAP (IT-40) or Blank-SAP (IT-21) was administered intrathecally at a single dose of 400 ng in 10 µL sterile saline to ablate spinal GRPR⁺ neurons involved in thermal and itch processing.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)