scholarly journals Activation of Two Different Drugs Used in Alzheimer’s Disease Treatment on Human Carbonic Anhydrase Isozymes I and II Activity: an In Vitro Study

2017 ◽  
Vol 14 (2) ◽  
pp. 164-168 ◽  
Author(s):  
Esra DiLEK
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Carbonic Anhydrase ◽  
Disease Treatment ◽  
Human Carbonic Anhydrase

scholarly journals Active Targeted Nanoemulsions for Repurposing of Tegaserod in Alzheimer’s Disease Treatment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1626
Author(s):  
Line Séguy ◽  
Léna Guyon ◽  
Manon Maurel ◽  
Pascal Verdié ◽  
Audrey Davis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Vitro Assays ◽  
Titration Calorimetry ◽  
Therapeutic Effects ◽  
Disease Treatment ◽  
Cellular Effects ◽  
Irritable Bowel ◽  
The Stability

Background and Purpose: The activation of 5-HT4 receptors with agonists has emerged as a valuable therapeutic strategy to treat Alzheimer’s disease (AD) by enhancing the nonamyloidogenic pathway. Here, the potential therapeutic effects of tegaserod, an effective agent for irritable bowel syndrome, were assessed for AD treatment. To envisage its efficient repurposing, tegaserod-loaded nanoemulsions were developed and functionalized by a blood–brain barrier shuttle peptide. Results: The butyrylcholinesterase inhibitory activity of tegaserod and its neuroprotective cellular effects were highlighted, confirming the interest of this pleiotropic drug for AD treatment. In regard to its drugability profile, and in order to limit its peripheral distribution after IV administration, its encapsulation into monodisperse lipid nanoemulsions (Tg-NEs) of about 50 nm, and with neutral zeta potential characteristics, was performed. The stability of the formulation in stock conditions at 4 °C and in blood biomimetic medium was established. The adsorption on Tg-NEs of peptide-22 was realized. The functionalized NEs were characterized by chromatographic methods (SEC and C18/HPLC) and isothermal titration calorimetry, attesting the efficiency of the adsorption. From in vitro assays, these nanocarriers appeared suitable for enabling tegaserod controlled release without hemolytic properties. Conclusion: The developed peptide-22 functionalized Tg-NEs appear as a valuable tool to allow exploration of the repurposed tegaserod in AD treatment in further preclinical studies.

scholarly journals A Snapshot on the Current Status of Alzheimer’s Disease, Treatment Perspectives, in-Vitro and in-Vivo Research Studies and Future Opportunities

2019 ◽  
Vol 67 (10) ◽  
pp. 1030-1041
Author(s):  
Gizem Tezel ◽  
Selin Seda Timur ◽  
İsmail Bozkurt ◽  
Ö. Faruk Türkoğlu ◽  
İpek Eroğlu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Current Status ◽  
Disease Treatment ◽  
Research Studies

scholarly journals Development of Novel Potential Pleiotropic Compounds of Interest in Alzheimer’s Disease Treatment through Rigidification Strategy

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2536
Author(s):  
Cédric Lecoutey ◽  
Rémi Legay ◽  
Audrey Davis ◽  
Jana Sopková-de Oliveira Santos ◽  
Patrick Dallemagne ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Stage ◽  
Receptor Agonist ◽  
Acetylcholinesterase Inhibitor ◽  
Structural Diversity ◽  
Docking Study ◽  
Disease Treatment ◽  
Ache Inhibitors

The development of Multi-Target Directed Ligand is of clear interest for the treatment of multifactorial pathology such as Alzheimer’s disease (AD). In this context, acetylcholinesterase (AChE) inhibitors have been modulated in order to generate novel pleiotropic compounds targeting a second protein of therapeutic interest in AD. Among them, donecopride was the first example of a dual acetylcholinesterase inhibitor and 5-HT4 receptor agonist. In order to explore the structural diversity around this preclinical candidate we have explored the preparation of novel constrained analogs through late-stage rigidification strategy. A series of phenylpyrazoles was prepared in a late-stage functionalization process and all compounds were evaluated in vitro towards AChE and 5-HTRs. A docking study was performed in order to better explain the observed SAR towards AChE, 5-HT4R and 5-HT6R and this study led to the description of novel ligand targeting both AChE and 5-HT6R.

scholarly journals Novel Perspective on Alzheimer’s Disease Treatment: Rosmarinic Acid Molecular Interplay with Copper(II) and Amyloid β

Life ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 118
Author(s):  
Arian Kola ◽  
Aleksandra Hecel ◽  
Stefania Lamponi ◽  
Daniela Valensin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rosmarinic Acid ◽  
Amyloid Β ◽  
Spectroscopic Techniques ◽  
Disease Treatment ◽  
Biological Assays ◽  
The Moment

Alzheimer’s disease is a severe disorder that affects millions of people worldwide. It is a very debilitating disease with no cure at the moment. The necessity of finding an effective treatment is very demanding, and the entire scientific community is putting in a lot of effort to address this issue. The major hallmark of Alzheimer’s disease is the presence of toxic aggregated species in the brain, impaired metal homeostasis, and high levels of oxidative stress. Rosmarinic acid is a well-known potent antioxidant molecule, the efficacy of which has been proved both in vitro and in vivo. In this study, we investigated the possible role played by rosmarinic acid as a mediator of the copper(II)-induced neurotoxicity. Several spectroscopic techniques and biological assays were applied to characterize the metal complexes and to evaluate the cytotoxicity and the mutagenicity of rosmarinic acid and its Cu(II) complex. Our data indicate that rosmarinic acid is able to interfere with the interaction between amyloid β and Cu(II) by forming an original ternary association.

Acetylcholinesterase Inhibitory Potential and Antioxidant Activities of Five Cultivars of Rosa Damascena Mill. From Isparta, Turkey

2020 ◽  
Vol 18 (4) ◽  
pp. 354-359
Author(s):  
Shirin Tarbiat ◽  
Azize Simay Türütoğlu ◽  
Merve Ekingen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radical ◽  
Neurodegenerative Disorder ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Acetylcholinesterase Activity ◽  
Rosa Damascena ◽  
Free Radical Damage

Alzheimer's disease is a neurodegenerative disorder characterized by memory loss and impairment of language. Alzheimer's disease is strongly associated with oxidative stress and impairment in the cholinergic pathway, which results in decreased levels of acetylcholine in certain areas of the brain. Hence, inhibition of acetylcholinesterase activity has been recognized as an acceptable treatment against Alzheimer's disease. Nature provides an array of bioactive compounds, which may protect against free radical damage and inhibit acetylcholinesterase activity. This study compares the in vitro antioxidant and anticholinesterase activities of hydroalcoholic extracts of five cultivars of Rosa Damascena Mill. petals (R. damascena 'Bulgarica', R. damascena 'Faik', R. damascena 'Iranica', R. damascena 'Complex-635' and R. damascena 'Complex-637') from Isparta, Turkey. The antioxidant activities of the hydroalcoholic extracts were tested for ferric ion reduction and DPPH radical scavenging activities. The anti-acetylcholinesterase activity was also evaluated. All rose cultivars showed a high potency for scavenging free radical and inhibiting acetylcholinesterase activity. There was a significant correlation between antioxidant and acetylcholinesterase inhibitory activity. Among cultivars, Complex-635 showed the highest inhibitory effect with an IC50 value of 3.92 µg/mL. Our results suggest that all these extracts may have the potential to treat Alzheimer's disease with Complex-635 showing more promise.

Natural Anti-inflammatory compounds as Drug candidates in Alzheimer’s disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Protective Action ◽  
New Drugs ◽  
Huperzine A ◽  
Brain Disorder ◽  
Anti Inflammatory

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.

In vivo Evaluation and Alzheimer’s Disease Treatment Outcome of siRNA Loaded Dual Targeting Drug Delivery System

2019 ◽  
Vol 20 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Chi Zhang ◽  
Zhichun Gu ◽  
Long Shen ◽  
Xianyan Liu ◽  
Houwen Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Outcome ◽  
Neuroprotective Effect ◽  
Sirna Delivery ◽  
Repeated Administration ◽  
Spatial Learning And Memory ◽  
In Vivo Evaluation

Background: To deliver drugs to treat Alzheimer’s Disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Methods: Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. In vivo, the treatment with ANNP/siRNA significantly improves the spatial learning and memory of APP/PS1 double transgenic mice, as determined by mean escape latency, times of crossing the platform area during the 60 s swimming and the percentage of the distance in the target quadrant. Results and Conclusion: After the treatment, BACE1 RNA level of ANNP/siRNA group was greatly reduced, which contributed a good AD treatment outcome. Finally, after repeated administration, the ANNP/siRNA did not lead to significant change as observed by HE staining of main organs, suggesting the good biocompatibility of ANNP/siRNA. These results demonstrated that the ANNP was a good candidate for AD targeting siRNA delivery.

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