Bexarotene cannot reduce amyloid beta plaques through inhibition of production of amyloid beta peptides:in silicoandin vitrostudy

2018 ◽  
Vol 20 (37) ◽  
pp. 24329-24338 ◽  
Author(s):  
Huy Dinh Quoc Pham ◽  
Nguyen Quoc Thai ◽  
Zuzana Bednarikova ◽  
Huynh Quang Linh ◽  
Zuzana Gazova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Amyloid Beta ◽  
Therapeutic Potential ◽  
Cancer Drug ◽  
Anti Cancer

Recently, it has been reported that anti-cancer drug bexarotene can remarkably destroy amyloid beta (Aβ) plaques in mouse models suggesting therapeutic potential for Alzheimer's disease.

Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer’s disease

2021 ◽  
Author(s):  
Ding-Yuan Tian ◽  
Yuan Cheng ◽  
Zhen-Qian Zhuang ◽  
Chen-Yang He ◽  
Qian-Guang Pan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Therapeutic Potential

scholarly journals Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease

2018 ◽  
Vol 527 (13) ◽  
pp. 2122-2145 ◽  
Author(s):  
Jennifer D. Whitesell ◽  
Alex R. Buckley ◽  
Joseph E. Knox ◽  
Leonard Kuan ◽  
Nile Graddis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Imaging ◽  
Mouse Models ◽  
Spatial Patterns ◽  
Amyloid Beta ◽  
Whole Brain

scholarly journals Blood lactate dynamics in awake and anaesthetized mice after intraperitoneal and subcutaneous injections of lactate—sex matters

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8328
Author(s):  
Øyvind P. Haugen ◽  
Evan M. Vallenari ◽  
Imen Belhaj ◽  
Milada Cvancarova Småstuen ◽  
Jon Storm-Mathisen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Lactate ◽  
Mouse Models ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
High Intensity Training ◽  
Significant Difference ◽  
5Xfad Mouse ◽  
Lactate Levels

Lactate treatment has shown a therapeutic potential for several neurological diseases, including Alzheimer’s disease. In order to optimize the administration of lactate for studies in mouse models, we compared blood lactate dynamics after intraperitoneal (IP) and subcutaneous (SC) injections. We used the 5xFAD mouse model for familial Alzheimer’s disease and performed the experiments in both awake and anaesthetized mice. Blood glucose was used as an indication of the hepatic conversion of lactate. In awake mice, both injection routes resulted in high blood lactate levels, mimicking levels reached during high-intensity training. In anaesthetized mice, SC injections resulted in significantly lower lactate levels compared to IP injections. Interestingly, we observed that awake males had significantly higher lactate levels than awake females, while the opposite sex difference was observed during anaesthesia. We did not find any significant difference between transgenic and wild-type mice and therefore believe that our results can be generalized to other mouse models. These results should be considered when planning experiments using lactate treatment in mice.

scholarly journals Mis-expression of the Alzheimer’s disease associated gene Ankyrin causes memory loss and shortened lifespan in Drosophila

2018 ◽  
Author(s):  
James P Higham ◽  
Bilal R Malik ◽  
Edgar Buhl ◽  
Jenny Dawson ◽  
Anna S Ogier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Neuronal Excitability ◽  
Therapeutic Potential ◽  
Association Studies ◽  
Treatment Options ◽  
Memory Loss ◽  
Normal Function ◽  
Mutant Proteins

ABSTRACTAlzheimer’s disease (AD) is the most common form of dementia and is characterized by the accumulation of extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles of hyperphosphorylated Tau, including the 4R0N isoform. Recent epigenome-wide association studies (EWAS) of AD have identified a number of loci that are differentially methylated in AD cortex. Indeed, hypermethylation of the Ankyrin 1 (ANK1) gene in AD has been reported in the cortex in numerous different post-mortem brain cohorts. Little is known about the normal function of ANK1 in the healthy brain, nor the role it may play in AD. We have generated Drosophila models to allow us to functionally characterize Drosophila Ank2, the ortholog of human ANK1. These models have targeted reduction in the expression of Ank2 in neurons. We find that Drosophila with reduced neuronal Ank2 expression have shortened lifespan, reduced locomotion, reduced memory and reduced neuronal excitability similar to flies overexpressing either human mutant APP (that leads to Aβ42 production) and MAPT (that leads to 0N4R Tau). Therefore, we show that the mis-expression of Ank2 can drive disease relevant processes and phenocopy some features of AD and we propose targeting ANK1 may have therapeutic potential. This represents the first study to characterize a gene implicated in AD, which was nominated from EWAS.Author summaryThe majority (>95%) of Alzheimer’s disease (AD) cases are sporadic, with their incidence attributed to common genetic mutations, epigenetic variation, aging and the environment. There is no cure for AD and only limited treatment options which only treat the symptoms of AD and only work in some people. Recent epigenome-wide association studies (EWAS) in AD have highlighted hypermethylation of the Ankyrin1 (ANK1) gene in AD cortex. Little is known of the normal role of the gene in the brain. Here, we have demonstrated that Drosophila with reduced neuronal expression of the Drosophila ortholog of human ANK1 (Ank2), can drive AD relevant processes including locomotor difficulties, memory loss and shortened lifespan similar to expression of human amyloid-Beta or tau mutant proteins. Furthermore, increasing Ank2 expression reversed the memory loss caused by expression of human amyloid-Beta or tau mutant proteins, suggesting that targeting ANK1 may have therapeutic potential. This represents the first study to characterize a gene implicated in AD, which was nominated from EWAS.

A bifunctional non-natural tetrapeptide modulates amyloid-beta peptide aggregation in the presence of Cu(ii)

Metallomics ◽  
2014 ◽  
Vol 6 (12) ◽  
pp. 2189-2192 ◽  
Author(s):  
Maripaz Márquez ◽  
Luis M. Blancas-Mejía ◽  
Adriana Campos ◽  
Luis Rojas ◽  
Gilberto Castañeda-Hernández ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Therapeutic Potential ◽  
Amyloid Beta Peptide ◽  
Peptide Aggregation ◽  
Beta Peptide ◽  
Aβ Aggregation

A novel bifunctional non-natural tetrapeptide, Met-Asp-d-Trp-Aib, is capable of binding copper, competing with amyloid-beta peptide (Aβ) for Cu(ii), and modulating Aβ aggregation. The study of this tetrapeptide provides further insights into the role of Cu(ii) in the Aβ aggregation pathway, and into the design of compounds with therapeutic potential for Alzheimer's disease.

scholarly journals Mutual Interactions between Brain States and Alzheimer’s Disease Pathology: A Focus on Gamma and Slow Oscillations

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 707
Author(s):  
Nicole Byron ◽  
Anna Semenova ◽  
Shuzo Sakata
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Therapeutic Potential ◽  
Brain Diseases ◽  
Pharmacological Intervention ◽  
Brain State ◽  
Population Activity ◽  
Slow Oscillations ◽  
Brain States

Brain state varies from moment to moment. While brain state can be defined by ongoing neuronal population activity, such as neuronal oscillations, this is tightly coupled with certain behavioural or vigilant states. In recent decades, abnormalities in brain state have been recognised as biomarkers of various brain diseases and disorders. Intriguingly, accumulating evidence also demonstrates mutual interactions between brain states and disease pathologies: while abnormalities in brain state arise during disease progression, manipulations of brain state can modify disease pathology, suggesting a therapeutic potential. In this review, by focusing on Alzheimer’s disease (AD), the most common form of dementia, we provide an overview of how brain states change in AD patients and mouse models, and how controlling brain states can modify AD pathology. Specifically, we summarise the relationship between AD and changes in gamma and slow oscillations. As pathological changes in these oscillations correlate with AD pathology, manipulations of either gamma or slow oscillations can modify AD pathology in mouse models. We argue that neuromodulation approaches to target brain states are a promising non-pharmacological intervention for neurodegenerative diseases.

P4-225: WHOLE BRAIN IMAGING REVEALS DISTINCT SPATIAL PATTERNS OF AMYLOID BETA DEPOSITION AND ATROPHY IN MOUSE MODELS OF ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_29) ◽  
pp. P1528-P1529
Author(s):  
Jennifer D. Whitesell ◽  
Alex R. Buckley ◽  
Nile Graddis ◽  
Leonard Kuan ◽  
Joseph E. Knox ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Imaging ◽  
Mouse Models ◽  
Spatial Patterns ◽  
Amyloid Beta ◽  
Whole Brain
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