ArticleCurrent Alzheimer research2015
Beneficial effects of the β-secretase inhibitor GRL-8234 in 5XFAD Alzheimer's transgenic mice lessen during disease progression.
Article in Current Alzheimer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Inhibition of Amyloid β Accumulation by Protease-Digested Whitebait (Shirasu) in a Murine Model of Alzheimer's Disease.Foods (Basel, Switzerland) · 2024Article
- Combination strategy employing BACE1 inhibitor and memantine to boost cognitive benefits in Alzheimer's disease therapy.Psychopharmacology · 2024Article
- Transgenic amyloid precursor protein mouse models of amyloidosis. Incomplete models for Alzheimer's disease but effective predictors of anti-amyloid therapies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Identification of potential marine bioactive compounds from brown seaweeds towards BACE1 inhibitors: molecular docking and molecular dynamics simulations approach.In silico pharmacology · 2024Article
- Characterization of apathy-like behaviors in the 5xFAD mouse model of Alzheimer's disease.Neurobiology of aging · 2023Article
- ARL6IP1 mediates small-molecule-induced alleviation of Alzheimer pathology through FXR1-dependent BACE1 translation initiation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Anti-malaria drug artesunate prevents development of amyloid-β pathology in mice by upregulating PICALM at the blood-brain barrier.Molecular neurodegeneration · 2023Article
- Accelerated long-term forgetting: A sensitive paradigm for detecting subtle cognitive impairment and evaluating BACE1 inhibitor efficacy in preclinical Alzheimer's disease.Frontiers in dementia · 2023Review
- Effects of Striatal Amyloidosis on the Dopaminergic System and Behavior: A Comparative Study in Male and Female 5XFAD Mice.Journal of Alzheimer's disease : JAD · 2023Article
- Accelerated long-term forgetting is a BACE1 inhibitor-reversible incipient cognitive phenotype in Alzheimer's disease model mice.Neuropsychopharmacology reports · 2021Article
- Article
- 3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice.The Journal of experimental medicine · 2019Article
- A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model.Scientific reports · 2018Article
- BACE1 inhibition more effectively suppresses initiation than progression of β-amyloid pathology.Acta neuropathologica · 2018Article
- Article
- Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer's disease.Neuroscience and biobehavioral reviews · 2016Review
- Longitudinal measures of cognition in the Ts65Dn mouse: Refining windows and defining modalities for therapeutic intervention in Down syndrome.Experimental neurology · 2016Article
- Effects of BACE1 haploinsufficiency on APP processing and Aβ concentrations in male and female 5XFAD Alzheimer mice at different disease stages.Neuroscience · 2015Article
- A combination Alzheimer's therapy targeting BACE1 and neprilysin in 5XFAD transgenic mice.Molecular brain · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The β-secretase enzyme BACE1, which initiates the cleavage of amyloid precursor protein (APP) into the amyloid-β (Aβ) peptide, is a prime therapeutic target for Alzheimer's disease (AD). However, recent investigations using genetic animal models raise concern that therapeutic BACE1 inhibition may encounter the dramatic reduction of efficacy in ameliorating AD-like pathology and memory deficits during disease progression. Here, we compared the effects of the potent and selective small-molecule BACE1 inhibitor GRL-8234 in different pathological stages of AD mouse model. Specifically, we administered GRL-8234 (33.4 mg/kg, i.p.) once daily for 2 months to 5XFAD transgenic mice, which showed modest (4 months) and massive (10 months of age) Aβ plaque deposition at starting points. Chronic treatments with GRL-8234 reversed memory impairments, as tested by the spontaneous alternation Y-maze task, in the younger 5XFAD group concomitant with significant reductions in cerebral Aβ42 levels. In contrast, only marginal reductions of Aβ42 were observed in 12-month-old 5XFAD mice treated with GRL-8234 and their memory function remained impaired. We found that not only BACE1 but also full-length APP expression was significantly elevated with progressive Aβ accumulation in 5XFAD mice, while GRL-8234 failed to affect these detrimental mechanisms that further accelerate plaque growth in brains of older 5XFAD mice. Therefore, our results provide important insights into the mechanisms by which Aβ accumulation and related memory impairments become less responsive to rescue by BACE1 inhibition during the course of AD development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.