Treating transgenic Alzheimer mice with a β-secretase inhibitor, what have we learned?

Tang, Jordan; Ghosh, Arun K.

doi:10.18632/aging.100267

Cited by 13 publications

(10 citation statements)

References 3 publications

(3 reference statements)

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“…Due to the structural properties, elevated BBB permeation and low molecular mass of KMI-429, it could show better actions than the standard reference [ 2 ]. The therapeutic role of β-secretase inhibitors in the reduction of Aβ is displayed by previous investigations in animal models in which the absence of the β-secretase gene caused only minor alterations in the phenotypic behavior of mice [ 53 ].…”

Section: Therapeutic Agents Targeting Amyloid Cascade Eventsmentioning

confidence: 99%

Exploring the Potential of Therapeutic Agents Targeted towards Mitigating the Events Associated with Amyloid-β Cascade in Alzheimer’s Disease

Behl

Kaur

Frățilă

et al. 2020

IJMS

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One of the most commonly occurring neurodegenerative disorders, Alzheimer’s disease (AD), encompasses the loss of cognitive and memory potential, impaired learning, dementia and behavioral defects, and has been prevalent since the 1900s. The accelerating occurrence of AD is expected to reach 65.7 million by 2030. The disease results in neural atrophy and disrupted inter-neuronal connections. Amongst multiple AD pathogenesis hypotheses, the amyloid beta (Aβ) cascade is the most relevant and accepted form of the hypothesis, which suggests that Aβ monomers are formed as a result of the cleavage of amyloid precursor protein (APP), followed by the conversion of these monomers to toxic oligomers, which in turn develop β-sheets, fibrils and plaques. The review targets the events in the amyloid hypothesis and elaborates suitable therapeutic agents that function by hindering the steps of plaque formation and lowering Aβ levels in the brain. The authors discuss treatment possibilities, including the inhibition of β- and γ-secretase-mediated enzymatic cleavage of APP, the immune response generating active immunotherapy and passive immunotherapeutic approaches targeting monoclonal antibodies towards Aβ aggregates, the removal of amyloid aggregates by the activation of enzymatic pathways or the regulation of Aβ circulation, glucagon-like peptide-1 (GLP-1)-mediated curbed accumulation and the neurotoxic potential of Aβ aggregates, bapineuzumab-mediated vascular permeability alterations, statin-mediated Aβ peptide degradation, the potential role of ibuprofen and the significance of natural drugs and dyes in hindering the amyloid cascade events. Thus, the authors aim to highlight the treatment perspective, targeting the amyloid hypothesis, while simultaneously emphasizing the need to conduct further investigations, in order to provide an opportunity to neurologists to develop novel and reliable treatment therapies for the retardation of AD progression.

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Section: Therapeutic Agents Targeting Amyloid Cascade Eventsmentioning

confidence: 99%

Exploring the Potential of Therapeutic Agents Targeted towards Mitigating the Events Associated with Amyloid-β Cascade in Alzheimer’s Disease

Behl

Kaur

Frățilă

et al. 2020

IJMS

View full text Add to dashboard Cite

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“…However, we have reported a time-dependent development of cerebral amyloid angiopathy in the STZ-icv treated rats (Salkovic-Petrisic et al 2011), indicating that amyloid pathology should be more extensively explored and characterized in this model, which may then be hopefully exploited in the novel anti-AD drug testing. Until now, data is available from the experiments on transgenic mice AD models only (Dodart et al 2002;Oddo et al 2006;Tang and Ghosh 2011), while these novel strategies have not been explored in the STZ-icv animal models.…”

Section: Other Therapeutic Strategiesmentioning

confidence: 99%

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

et al. 2012

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“…21,22 Transgenic/mutant strains of mice and rats with overproduction of AβPP, presenilin, tau protein, and ApoE cannot provide an all-encompassing picture of the pathophysiology of AD. 23,24 Moreover, all these models are characterized by an increased expression of genes and mutations that are typical in early onset eXTRA viewS Review Figure 1. Quantification of neuronal populations in the hippocampal CA3 region of OXYS rats.…”

Section: Introductionmentioning

confidence: 99%

Senescence-accelerated OXYS rats: A model of age-related cognitive decline with relevance to abnormalities in Alzheimer disease

et al. 2014

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Senescence-accelerated OXYS rats are an experimental model of accelerated aging that was established from wistar stock via selection for susceptibility to cataractogenic effects of a galactose-rich diet and via subsequent inbreeding of highly susceptible rats. Currently, we have the 102nd generation of OXYS rats with spontaneously developing cataract and accelerated senescence syndrome, which means early development of a phenotype similar to human geriatric disorders, including accelerated brain aging. in recent years, our group found strong evidence that OXYS rats are a promising model for studies of the mechanisms of brain aging and neurodegenerative processes similar to those seen in Alzheimer disease (AD). The manifestation of behavioral alterations and learning and memory deficits develop since the fourth week of age, i.e., simultaneously with first signs of neurodegeneration detectable on magnetic resonance imaging and under a light microscope. in addition, impaired long-term potentiation has been demonstrated in OXYS rats by the age of 3 months. with age, neurodegenerative changes in the brain of OXYS rats become amplified. we have shown that this deterioration happens against the background of overproduction of amyloid precursor protein (AβPP), accumulation of β-amyloid (Aβ), and hyperphosphorylation of the tau protein in the hippocampus and cortex. The development of AMDlike retinopathy in OXYS rats is also accompanied by increased accumulation of Aβ in the retina. These published data suggest that the OXYS strain may serve as a spontaneous rat model of AD-like pathology and could help to decipher the pathogenesis of AD.

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Treating transgenic Alzheimer mice with a β-secretase inhibitor, what have we learned?

Cited by 13 publications

References 3 publications

Exploring the Potential of Therapeutic Agents Targeted towards Mitigating the Events Associated with Amyloid-β Cascade in Alzheimer’s Disease

Exploring the Potential of Therapeutic Agents Targeted towards Mitigating the Events Associated with Amyloid-β Cascade in Alzheimer’s Disease

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

Senescence-accelerated OXYS rats: A model of age-related cognitive decline with relevance to abnormalities in Alzheimer disease

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