alzheimers-disease

Björklund A, Barker RA (2024) The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson’s disease. Brain awae026. doi: 10.1093/brain/awae026 PMID: 38279949

Objective: Review the use of cholinergic cell replacement as a potential therapeutic strategy in Parkinson’s Disease (PD) and how rodent models of PD-like cognitive decline can be used by analyzing rodent and primate studies.

Summary: Although therapies targeting the cholinergic system have so far been focused mainly on patients with Alzheimer´s disease, PD with dementia may be a more relevant condition. In PD with dementia the Basal Forebrain system undergoes progressive degeneration, and the magnitude of cholinergic cell loss has been shown to correlate with the level of cognitive impairment. Thus, cell therapy aimed to replace the lost basal forebrain cholinergic neurons represents an interesting strategy to combat some of the major cognitive impairments in patients with PD dementia.

Usage: Rats were given 192-IgG-SAP (IT-01), 0.2-0.4 μg, delivered as a single 0.3-1.0 μl injection into either the substantia innominate/nucleus basalis of Meynert (SI/NBM) or the medial septum/ventral diagonal band (MS/VDB).

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

Matynia A, Recio BS, Myers Z, Parikh S, Goit RK, Brecha NC, Pérez de Sevilla Müller L (2024) Preservation of intrinsically photosensitive retinal ganglion cells (ipRGCs) in late adult mice: Implications as a potential biomarker for early onset ocular degenerative diseases. Invest Ophthalmol Vis Sci 65(1):28. doi: 10.1167/iovs.65.1.28 PMID: 38224335

Objective: To assess the preservation of intrinsically photosensitive retinal ganglion cells (ipRGCs) in late adult mice and evaluate their potential as biomarkers for early onset ocular degenerative diseases.

Summary: This study investigates the stability of ipRGC morphology and function in mice aged 6 to 12 months, revealing that ipRGCs maintain their dendritic complexity and associated behavioral functions, such as pupillary light reflex and contrast sensitivity, during this period. These findings suggest that the consistent preservation of ipRGCs in late adulthood may serve as a valuable biomarker for early detection of ocular degenerative diseases, including Alzheimer’s, Parkinson’s, and diabetes.

Usage: Whole mount retinas were incubated with Anti-Melanopsin (AB-N39) at 1:1000 for 7 days at 4°C.

Related Products: Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39)

Wu D, Yu N, Gao Y, Xiong R, Liu L, Lei H, Jin S, Liu J, Liu Y, Xie J, Liu E, Zhou Q, Liu Y, Li S, Wei L, Lv J, Yu H, Zeng W, Zhou Q, Xu F, Luo MH, Zhang Y, Yang Y, Wang JZ (2023) Targeting a vulnerable septum-hippocampus cholinergic circuit in a critical time window ameliorates tau-impaired memory consolidation. Mol Neurodegener 18(1):23. doi: 10.1186/s13024-023-00614-7 PMID: 37060096

Objective: There is an urgent need to study the targeting strategy for the MS-hippocampus cholinergic pathway to rescue tau-impaired memory.

Summary: Abnormal tau accumulation and cholinergic degeneration are hallmark pathologies in the brains of patients with Alzheimer’s disease (AD). However, the sensitivity of cholinergic neurons to AD-like tau accumulation and strategies to ameliorate tau-disrupted spatial memory in terms of neural circuits still remain elusive. The authors found that cholinergic neurons with an asymmetric discharge characteristic in the MS-hippocampal CA1 pathway are vulnerable to tau accumulation. Photoactivating MS-CA1 cholinergic inputs within a critical 3 h time window during memory consolidation efficiently improved tau-induced spatial memory deficits in a theta rhythm dependent manner. 192-IgG-Saporin was used to create an Alzheimer’s Disease animal model.

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

See Also:

• Dornan WA et al. Comparison of site-specific injections into the basal forebrain on water maze and radial arm maze performance in the male rat after immunolesioning with 192 IgG saporin. Behav Brain Res 82:93-101, 1996.

Singh SA, Vellapandian C (2023) The promising guide to LC–MS analysis and cholinesterase activity of Luffa cylindrica (L.) fruit using in vitro and in-silico analyses. Futur J Pharm Sci 9:33. doi: 10.1186/s43094-023-00478-0

Objective: Identify and analyze the extract of the plant Luffa cylindrica for bioactive and biochemical properties, particularly as it relates to bioactivity in neurological diseases.

Summary: Luffa cylindrica contains a total of 80 compounds that were identified in the ethanolic extract from LC–MS analysis. The bioactive compounds were screened for activity in receptors responsible for causing oxidative stress-associated Alzheimer’s disease. Perlolyrine was chosen to perform in-silico docking. An in vitro activity of cholinesterase showed highest inhibition at 500 μg/ml. In-silico docking of perlolyrine showed better binding affinity and score. Results revealed that out of 10 docked receptors, amyloid beta showed the highest binding affinity with an energy of −46.1 kcal/mol showing promising drug for Alzheimer’s disease. The study reports the presence of a promising, bioactive compound (perlolyrine) with promisng applications in vivo, oxidative stress-related Alzheimer’s disease.

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

See Also:

• Santosh et al (2015) Mechanism of Anti-HIV Activity of Ribosome Inactivating Protein, Saporin. Protein & Peptide Letters. 22(6): 497-503. doi: 10.2174/0929866522666150428120701

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)

Silva AR (2022) Uncovering central and peripheral pain mechanisms in Alzheimer’s disease. King’s College London Thesis.

Objective: To investigate alterations within the nociceptive pathways, under neuropathic pain conditions.

Summary: The data suggest a disrupted opioidergic tone in TASTPM mice, which followed by peripheral nerve injury, is mediated by peripheral immune cells.

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

See Also:

• Brightwell JJ et al. Noradrenergic neurons in the locus coeruleus contribute to neuropathic pain. Neuroscience 160:174-185, 2009.

Zhou XA, Ngiam G, Qian L, Sankorrakul K, Coulson EJ, Chuang KH (2022) The basal forebrain volume reduction detected by MRI does not necessarily link with the cholinergic neuronal loss in the Alzheimer’s disease mouse model. Neurobiol Aging 117:24-32. doi: 10.1016/j.neurobiolaging.2022.03.017 PMID: 35640461

Objective: Assess basal forebrain (BF) cholinergic neuron number by histological counts and compare with the volume measurements from an in vivo MRI Alzheimer’s disease (AD) mouse model.

Summary: Degeneration of cholinergic neurons in the BF contributes to cognitive impairment in AD. A decrease of BF volume measured by structural MRI is thought to represent loss of cholinergic neurons. As there are various types of neurons in the BF, whether this MRI measurement actually reflects the change of cholinergic neurons has not been verified. To test whether specific loss of cholinergic neurons results in BF reduction, the authors ablated cholinergic neurons in the Medial septum.

Usage: Lesions were made via injections of mu-p75-SAP (0.5 mg/ml) or control Rabbit-IgG-SAP (0.5 mg/mL) into ten-week-old female C57Bl/6J mice. However, there was no detectable change in MRI volume between lesioned and unlesioned mice. The results indicate that although loss of cholinergic neurons within the BF likely contribute to volume loss, this change in volume cannot be taken as a direct biomarker of cholinergic neuron number.

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

Llorente-Ovejero A, Bengoetxea de Tena I, Martínez-Gardeazabal J, Moreno-Rodríguez M, Lombardero L, Manuel I, Rodríguez-Puertas R (2022) Cannabinoid receptors and glial response following a basal forebrain cholinergic lesion. ACS Pharmacol Transl Sci 5(9):791-802. doi: 10.1021/acsptsci.2c00069 PMID: 36110372

Objective: The endocannabinoid system is involved in the control of learning, memory, and neuroinflammatory processes and plays a role in neurodegeneration, such as in Alzheimer’s disease (AD). The objective was to study the roles of cannabinoid receptors in the regulation of neuroinflammation.

Summary: Selective agonists and antagonists to the cannabinoid receptors CB1 and CB2 were studied for their binding to G-proteins after specific lesioning of the basal forebrain cholinergic neurons (BCFN) using 192-IgG-SAP. These neurons are the same cholinergic pathways that are lost in the early stages of Alzheimer’s disease (AD). In their study, an increase of microglia immunoreactivities (GFAP and Iba-1) and decrease of astrocyte immunoreactivities were seen which indicate microglia-mediated neuroinflammation. In cortical BFCN projection areas, CB1 receptor binding to Gi/o-proteins was upregulated and at the injection site, the area that showed the highest increase of microglia, only slight CB2 binding to Gi/o-proteins were detected. Dose: Rats received 135 ng/μLof 192IgG-saporin (1μL/hemisphere; 0.25μL/min).

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

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.

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 PMID: 35324681

Summary: Saporin is a ribosome-inactivating protein that can cause inhibition of protein synthesis and causes cell death when delivered inside a cell. Development of commercial Saporin results in a technology termed ‘molecular surgery’, with Saporin as the scalpel. Its low toxicity (it has no efficient method of cell entry) and sturdy structure make Saporin a safe and simple molecule for many purposes. The most popular applications use experimental molecules that deliver Saporin via an add-on targeting molecule. These add-ons come in several forms: peptides, protein ligands, antibodies, even DNA fragments that mimic cell-binding ligands. Cells that do not express the targeted cell surface marker will not be affected. This review will highlight some newer efforts and discuss significant and unexpected impacts on science that molecular surgery has yielded over the last almost four decades. There are remarkable changes in fields such as the Neurosciences with models for Alzheimer’s Disease and epilepsy, and game-changing effects in the study of pain and itch. Many other uses are also discussed to record the wide-reaching impact of Saporin in research and drug development.

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