References

Morroni F, Caccamo A (2024) Advances and Challenges in Gene Therapy for Alzheimer’s Disease. J Alzheimers Dis 101(s1):S417-S431. doi: 10.3233/JAD-230783 PMID: 39422937

Objective: Provide an overview of clinical and preclinical studies where gene therapy techniques have been utilized in the context of Alzheimer’s Disease (AD), highlighting their potential as novel therapeutic strategies.

Summary: Gene therapy offers the potential for long-term benefits by providing sustained therapeutic effects. By modifying or replacing faulty genes, it may slow down or halt the progression of AD. Vector-based genetic therapies have demonstrated promising results in mouse models, but face hurdles such as managing risks associated with vectors and delivery methods.

Usage: Rats with cholinergic deficit were induced by intraseptal injection of 192-IgG-SAP (IT-01).

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

See Also:

• Dobryakova YV et al. Intrahippocampal adeno-associated virus-mediated overexpression of nerve growth factor reverses 192IgG-saporin-induced impairments of hippocampal plasticity and behavior. Front Neurosci 15:745050, 2021.

Aerts EG (2024) Estradiol’s role in timely puberty onset in the ewe. Western Virginia Univ

Objective: To investigate the role of arcuate nucleus KNDy (kisspeptin/neurokinin B/dynorphin) neurons in regulating the timing of puberty onset and estradiol (E2) sensitivity in female sheep.

Summary: Ablation of approximately 75% of KNDy neurons using NKB-SAP in the arcuate nucleus significantly delayed puberty onset and blunted the luteinizing hormone (LH) surge, demonstrating that KNDy neurons are critical for timely puberty in ewes. However, animals retained the ability to respond to NK3R agonist senktide, suggesting upstream populations may mediate estradiol negative feedback.

Usage: NKB-SAP (IT-63) was bilaterally injected into the arcuate nucleus (1 µg/side in 1 µL) to ablate NK3R-expressing KNDy neurons and evaluate their role in pubertal timing and LH regulation.

Related Products: NKB-SAP (Cat. #IT-63)

Chen S (2024) Nanocapsule-based prodrugs for targeted treatment of AIDS-associated non-hodgkin lymphoma. Univ California Thesis.

Objective: To propose a novel nanocapsule based platform that encapsulates the native drugs using various monomers and crosslinkers through free radical polymerization.

Summary: This encapsulation technology modifies the surface properties of the encapsulated drugs, enhancing their penetration into deeper tumor tissues and across the blood-brain barrier (BBB). Moreover, it significantly improves the stability of the drugs in vivo, protecting them from rapid degradation or clearance by the immune system. By adjusting the composition of the monomers and crosslinkers, the surface charge, hydrophobicity, and size of the nanocapsules can be finely tuned to maximize their efficacy in reaching and penetrating the target tissues.

Usage: Conjugation of ch128.1Av (anti-TfR1 IgG3-avidin fusion protein) with biotinylated saporin 6 (b-SO6) to eliminate malignant cells, including NHL malignancies. However, safe systemic delivery of ch128.1Av/b-SO6 is limited by its non-specific toxicity to normal cells expressing TfR1.

Related Products: MonoBiotin-ZAP (Cat. #BT-ZAP)

Thomson AC (2024) Puberty-Associated Changes in Kiss1r, MC3R, and MC4R in the Ewe. West Virgina University

Objective: To examine kisspeptin receptor (Kiss1r) mRNA expression in gonadotropin releasing hormone (GnRH) neurons and melanocortin 3 and 4 receptor (MC3R/MC4R) expression in kisspeptin neurons across pubertal development.

Summary: Kiss1r expression in GnRH neurons increased with development. In the arcuate nucleus (ARC), the proportion of kisspeptin neurons expressing MC3R, but not MC4R, also rose, though MC3R signal intensity remained unchanged. ARC Kiss1r expression did not vary. Findings support increased GnRH neuron sensitivity to kisspeptin and aMSH as part of the pubertal neurocircuitry.

Usage: Author references prior studies. Deletion of about 75% of KNDy neurons through targeted NKB-SAP (IT-63) injections significantly delayed puberty onset. Reduction of Kiss1r expression in the ARC via targeted injection of a Kisspeptin-SAP (IT-102) conjugate disrupted pulsatile LH release and blocked the LH surge.

Related Products: NKB-SAP (Cat. #IT-63)

See Also:

• Aerts EG et al. The effect of NK3-Saporin injection within the arcuate nucleus on puberty, the LH surge, and the response to Senktide in female sheep. Biol Reprod 110(2):275-287, 2024.

Edwards CM, Guerrero IE, Thompson D, Dolezel T, Rinaman L (2024) An ascending vagal sensory-central noradrenergic pathway modulates retrieval of passive avoidance memory. bioRxiv 2024.04.09.588717. doi: 10.1101/2024.04.09.588717 PMID: 38645069

Objective: To investigate the role of a gut vagal afferent-to-central noradrenergic pathway in modulating the retrieval of conditioned passive avoidance memory in rats.

Summary: This study explores how visceral sensory feedback via vagal afferents and central noradrenergic neurons influences passive avoidance memory retrieval. By lesioning specific neural pathways in adult male rats, the researchers demonstrate that disruption of these circuits significantly increased conditioned passive avoidance behavior, suggesting a critical role for these pathways in integrating interoceptive signals with contextual cues to modulate learned avoidance behaviors.

Usage: 250 ng of CCK-SAP (IT-31) was bilaterally injected into the nodose ganglion to selectively lesion gastrointestinal vagal afferents. 80 ng of Anti-DBH-SAP (IT-03) was injected bilaterally into the ventrolateral bed nucleus of the stria terminalis (vlBNST) to selectively lesion noradrenergic inputs to the anterior vlBNST.

Related Products: CCK-SAP (Cat. #IT-31), Anti-DBH-SAP (Cat. #IT-03)

Balukova A, Bokea K, Barber PR, Ameer-Beg SM, MacRobert AJ, Yaghini E (2024) Cellular imaging and time-domain FLIM studies of meso-tetraphenylporphine disulfonate as a photosensitising agent in 2D and 3D models. Int J Mol Sci 25(8):4222. doi: 10.3390/ijms25084222 PMID: 38673807

Objective: To investigate the uptake and subcellular localization of TPPS2a and evaluate the photooxidative mechanism using reactive oxygen species (ROS) and lipid peroxidation probes combined with appropriate ROS scavengers.

Summary: Overall, it can be concluded that the photophysical properties of TPPS2a in cells are not markedly perturbed and that the fluorescence lifetime behavior is consistent with that observed in model systems where both porphyrin monomers and aggregates are present.

Usage: Authors previously studied the PDT and PCI efficacy of TPPS2a in HEY cells in 2D and 3D spheroid models using saporin as the chemotherapeutic agent.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Hadi LM, Yaghini E, Stamati K, Loizidou M, MacRobert AJ. (2018) Therapeutic enhancement of a cytotoxic agent using photochemical internalisation in 3D compressed collagen constructs of ovarian cancer. Acta Biomater 81:80-92. doi: 10.1016/j.actbio.2018.09.041 PMID: 30267880
• Mohammad Hadi L, Stamati K, Yaghini E, MacRobert AJ, Loizidou M (2023) Treatment of 3D in vitro tumoroids of ovarian cancer using photochemical internalisation as a drug delivery method. Biomedicines 11(2):572. doi: 10.3390/biomedicines11020572 PMID: 36831108

Kumbhare D, Rajagopal M, Toms J, Freelin A, Weistroffer G, McComb N, Karnam S, Azghadi A, Murnane KS, Baron MS, Holloway KL (2024) Deep brain stimulation of nucleus basalis of meynert improves learning in rat model of dementia. bioRxiv 2024.04.05.588271. doi: 10.1101/2024.04.05.588271 PMID: 38645266

Objective: To assess the effects of varying stimulation patterns and duration on learning in a dementia rat model.

Summary: Deep brain stimulation (DBS) of nucleus basalis of Meynert (NBM) has been considered a potential treatment for dementia, but more study is needed to determine the ideal parameters for NBM stimulation. 192-IgG-SAP (Cat. IT-01) was used to lesion cholinergic neurons of rats creating a rat model of dementia upon which NBM deep brain stimulation could be tested. The desired destruction of neurons was 70-80% cholinergic population lesioned, which through a panel of concentrations was determined to be a 0.50 μg dose. The rat models of dementia were then tested for ideal type and duration of deep brain stimulation to improve operant learning test performance.

Usage: 192-IgG-SAP was bilaterally injected in the NBM in the following amounts: 0.00 (control), 0.15, 0.30, 0.50, and 0.75 μg in 0.5 μl PBS.

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

Choi PP, Wang Q, Brenner LA, Li AJ, Ritter RC, Appleyard SM (2024) Lesion of NPY receptor-expressing neurons in perifornical lateral hypothalamus attenuates glucoprivic feeding. Endocrinology 165(5):bqae021. doi: 10.1210/endocr/bqae021 PMID: 38368624

Objective: To explore the role of NPY receptor-expressing neurons in regulating feeding behavior in rats.

Summary: In response to glucose deficits, rats exhibit counter-regulatory mechanisms to stimulate feeding. To clarify the role of NPY-sensitive neurons, these neurons were selectively ablated using NPY-SAP. The results showed that while Saporin-lesioned rats exhibited reduced 2DG-induced feeding, there was no impact on 2DG-induced locomotor activity, sympathoadrenal hyperglycemia, or corticosterone release.

Usage: NPY-SAP [IT-28] or Blank-SAP [IT-21] (50 ng per 100nL/site) was used to specifically lesion NPY receptor-expressing neurons in the perifornical lateral hypothalamus of male rats.

Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)

Nord C, Jones I, Garcia-Maestre M, Hägglund AC, Carlsson L (2024) Reduced mTORC1-signaling in progenitor cells leads to retinal lamination deficits. Dev Dyn doi: 10.1002/dvdy.707 PMID: 38546215

Objective: To demonstrate that mTORC1 mediates critical roles during neuronal lamination using the mouse retina as a model system.

Summary: This study establishes a critical role for mTORC1-signaling during retinal lamination and demonstrates that this pathway regulates diverse developmental mechanisms involved in driving the stratified arrangement of neurons during CNS development.

Usage: Immunohistochemistry (AB-N38) (1:1000).

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

Huang M, Fang W, Farrel A, Li L, Chronopoulos A, Nasholm N, Cheng B, Zheng T, Yoda H, Barata MJ, Porras T, Miller ML, Zhen Q, Ghiglieri L, McHenry L, Wang L, Asgharzadeh S, Park J, Gustafson WC, Matthay KK, Maris JM, Weiss WA (2024) ALK upregulates POSTN and WNT signaling to drive neuroblastoma. Cell Rep 43(3):113927. doi: 10.1016/j.celrep.2024.113927 PMID: 38451815

Objective: To determine how anaplastic lymphoma kinase (ALK) contributes to tumor formation.

Summary: ALK partially drives neuroblastoma through a feedforward loop between POSTN and WNT signaling.

Usage: AB-N07 Anti-NGFR Immunofluorescence (1:250).

Related Products: NGFR (ME20.4, p75) Mouse Monoclonal (Cat. #AB-N07)