scholarly journals Experimental Therapeutic Effects of Hybrid Liposomes on the Alzheimer's Disease in Vitro

2011 ◽  
Vol 131 (5) ◽  
pp. 775-782 ◽  
Author(s):  
Keiko ZAKO ◽  
Maki SAKAGUCHI ◽  
Yuji KOMIZU ◽  
Hideaki ICHIHARA ◽  
Koichi GOTO ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Effects

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 Nepeta menthoides Boiss. & Buhse, an endemic species in Iran: A review of traditional uses, phytochemistry and pharmacology

2019 ◽  
Vol 8 (3) ◽  
pp. 194-204
Author(s):  
Zahra Memariani ◽  
Atena Rahimi ◽  
Mohammad Hosein Farzaei ◽  
Niloofar Zakaria Nejad
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endemic Species ◽  
Scientific Evidence ◽  
Therapeutic Effects ◽  
Lavandula Stoechas ◽  
Traditional Persian Medicine ◽  
Memory Enhancing

Nepeta menthoides Boiss & Buhse is one of the endemic species in Iran. Named Ostokhodus, it is almost used as substitute of the Lavandula stoechas –the original Ostokhodus- in traditional Persian medicine (TPM) over the time and widely used for the management of some ailments such as anxiety, depression, dementia and chronic pain. The aim of this study is to review the pharmacological and phytochemical evidence on Nepeta menthoides for the assessment of the recommended traditional indications of this herb. In this review, all the relevant articles that met our inclusion criteria [English or Persian articles, having full text, evaluating therapeutic effects of N. menthoides and dated mainly from the year 1980 to 2018] were included by searching studies in PubMed, Scopus, Google Scholar, Web of Science, and SID. The search terms were "Nepeta menthoides, "Ostokhodus". Triterpenes and monoterpenes were the most chemicals reported from essential oil of N. menthoides. Several pharmacological properties via in vitro, in vivo and clinical studies have been reported including antioxidant, anti-inflammatory, anti-nociceptive, antidepressant and anxiolytic, anticholinesterase, neuroprotective, memory enhancing, anti-Alzheimer’s disease, anticancer and effect on opioid dependence. Some proposed traditional indications of this herb in TPM books are in accordance with pharmacological evidence like anti-nociceptive, anti-seizure, anti-Alzheimer’s disease, memory enhancing, neuroprotective, antidepressant, anxiolytic activity and anti-infective properties. Although some properties in TPM, such as anti-tussive and gastrotonic effects are not supported by scientific evidence, they need more investigations.

scholarly journals Neurotrophin-3 Promotes the Neuronal Differentiation of BMSCs and Improves Cognitive Function in a Rat Model of Alzheimer's Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Zhongrui Yan ◽  
Xianjing Shi ◽  
Hui Wang ◽  
Cuiping Si ◽  
Qian Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Neuronal Differentiation ◽  
Molecular Mechanisms ◽  
Therapeutic Effects ◽  
Model Of Alzheimer’S Disease ◽  
Neurotrophin 3

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has the potential to be developed into an effective treatment for neurodegenerative diseases such as Alzheimer's disease (AD). However, the therapeutic effects of BMSCs are limited by their low neural differentiation rate. We transfected BMSCs with neurotrophin-3 (NT-3), a neurotrophic factor that promotes neuronal differentiation, and investigated the effects of NT-3 gene overexpression on the differentiation of BMSCs into neurons in vitro and in vivo. We further studied the possible molecular mechanisms. We found that overexpression of NT-3 promoted the differentiation of BMSCs into neurons in vitro and in vivo and improved cognitive function in rats with experimental AD. By contrast, silencing NT-3 inhibited the differentiation of BMSCs and decreased cognitive function in rats with AD. The Wnt/β-catenin signaling pathway was involved in the mechanism by which NT-3 gene modification influenced the neuronal differentiation of BMSCs in vitro and in vivo. Our findings support the prospect of using NT-3-transduced BMSCs for the development of novel therapies for AD.

scholarly journals N-Truncated Aβ Starting at Position Four—Biochemical Features, Preclinical Models, and Potential as Drug Target in Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Thomas A. Bayer
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Drug Target ◽  
Passive Immunization ◽  
Therapeutic Effects ◽  
Preclinical Models ◽  
Pyroglutamate Aβ

The discussion of whether amyloid plaque Aβ is a valid drug target to fight Alzheimer’s disease (AD) has been a matter of scientific dispute for decades. This question can only be settled by successful clinical trials and the approval of disease-modifying drugs. However, many clinical trials with antibodies against different regions of the amyloid Aβ peptide have been discontinued, as they did not meet the clinical endpoints required. Recently, passive immunization of AD patients with Donanemab, an antibody directed against the N-terminus of pyroglutamate Aβ, showed beneficial effects in a phase II trial, supporting the concept that N-truncated Aβ is a relevant target for AD therapy. There is long-standing evidence that N-truncated Aβ variants are the main variants found in amyloid plaques besides full-length Aβ1–42, t, therefore their role in triggering AD pathology and as targets for drug development are of interest. While the contribution of pyroglutamate Aβ3–42 to AD pathology has been well studied in the past, the potential role of Aβ4–42 has been largely neglected. The present review will therefore focus on Aβ4–42 as a possible drug target based on human and mouse pathology, in vitro and in vivo toxicity, and anti-Aβ4-X therapeutic effects in preclinical models.

scholarly journals Therapeutic Effects of Natural Compounds and Small Molecule Inhibitors Targeting Endoplasmic Reticulum Stress in Alzheimer’s Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Xun Gao ◽  
Yuanyuan Xu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Natural Compounds ◽  
Therapeutic Effects

Alzheimer’s disease (AD) is the most common neurodegenerative disease, characterized by progressive cognitive impairment and memory loss. So far, the pathogenesis of AD has not been fully understood. Research have shown that endoplasmic reticulum (ER) stress and unfolded protein response (UPR) participate in the occurrence and development of AD. Furthermore, various studies, both in vivo and in vitro, have shown that targeting ER stress and ER stress-mediated apoptosis contribute to the recovery of AD. Thus, targeting ER stress and ER stress-mediated apoptosis may be effective for treating AD. In this review, the molecular mechanism of ER stress and ER stress-mediated apoptosis, as well as the therapeutic effects of some natural compounds and small molecule inhibitors targeting ER stress and ER stress-mediated apoptosis in AD will be introduced.

scholarly journals A selective p38α/β MAPKs inhibitor alleviates neuropathology and cognitive impairment by modulating microglia function in 5XFAD mouse

2020 ◽  
Author(s):  
Min Sung Gee ◽  
Seung Hwan Son ◽  
Seung Ho Jeon ◽  
Jimin Do ◽  
Namkwon Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Conditioned Medium ◽  
In Vitro Studies ◽  
Therapeutic Effects ◽  
5Xfad Mice ◽  
Ad Therapy ◽  
P38 Mapks

Abstract Background: Chronic neuroinflammation, aggressive amyloid beta (Aβ) deposition, neuronal cell loss and cognitive impairment are pathological symptoms of Alzheimer’s disease (AD). Regarding these symptoms, resolution of neuroinflammation and inhibition of Aβ-driven pathology might be one of the important strategies for AD therapy. Previous efforts to prevent AD progression have identified that p38 mitogen-activated protein kinase (MAPK) is a promising target for AD therapy. Especially, recent studies showed that pharmacological p38α MAPK inhibition improved memory impairment in AD mouse models. Methods: In this study, we explored the therapeutic potential of NJK14047, a selective p38α/β MAPKs inhibitor, using an Alzheimer’s disease mouse model, 5XFAD. The mice were injected 2.5 mg/kg NJK14047 or vehicle every other day for 3 months. Morris water maze task and histological imaging analysis were performed. Protein and mRNA expression levels were measured using immunoblotting and qRT-PCR respectively. In in vitro studies, the cytotoxicity of microglial conditioned medium and astrocyte conditioned medium on primary neurons were measured using MTT assay and TUNEL assay. Results: NJK14047 treatment downregulated phospho-p38 MAPK levels, decreased the amount of Aβ deposits, and prevented spatial learning memory loss in 9-month-old 5XFAD mice. Interestingly, we found the decreased pro-inflammatory conditions and increased expression of alternatively activated microglial markers and microglial phagocytic receptors. Furthermore, NJK14047 treatment reduced the number of Fluoro-jade B positive cells, a class of degenerating neurons, in the brains of 5XFAD mice. The neuroprotective effect of NJK14047 was further confirmed by in vitro studies. Conclusion: Taken together, a selective p38α/β MAPKs inhibitor NJK14047 successfully showed therapeutic effects in 5XFAD mice. Our data support that p38 MAPKs inhibition is a potential strategy for AD therapy and NJK14047 might be one of the promising candidates for AD therapeutics targeting p38 MAPKs.

scholarly journals A selective p38α/β MAPKs inhibitor alleviates neuropathology and cognitive impairment, and modulates microglia function in 5XFAD mouse

2020 ◽  
Author(s):  
Min Sung Gee ◽  
Seung Hwan Son ◽  
Seung Ho Jeon ◽  
Jimin Do ◽  
Namkwon Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
In Vitro Studies ◽  
Therapeutic Effects ◽  
Mitogen Activated Protein ◽  
5Xfad Mice ◽  
Ad Therapy ◽  
P38 Mapks

Abstract Background: Chronic neuroinflammation, aggressive amyloid beta (Aβ) deposition, neuronal cell loss, and cognitive impairment are pathological presentations of Alzheimer’s disease (AD). Therefore, resolution of neuroinflammation and inhibition of Aβ-driven pathology have been suggested to be important strategies for AD therapy. Previous efforts to prevent AD progression have identified p38 mitogen-activated protein kinases (MAPKs) as a promising target for AD therapy. Recent studies showed pharmacological inhibition of p38α MAPK improved memory impairment in AD mouse models. Methods: In this study, we used an AD mouse model, 5XFAD, to explore the therapeutic potential of NJK14047 which is a novel, selective p38α/β MAPKs inhibitor. The mice were injected with 2.5 mg/kg NJK14047 or vehicle every other day for 3 months. Morris water maze task and histological imaging analysis were performed. Protein and mRNA expression levels were measured using immunoblotting and qRT-PCR, respectively. In vitro studies were conducted to measure the cytotoxicity of microglia- and astrocyte-conditioned medium on primary neurons using the MTT assay and TUNEL assay. Results: NJK14047 treatment downregulated phospho-p38 MAPK levels, decreased the amount of Aβ deposits, and reduced spatial learning memory loss in 9-month-old 5XFAD mice. While the pro-inflammatory conditions were decreased, the expression of alternatively activated microglial markers and microglial phagocytic receptors was increased. Furthermore, NJK14047 treatment reduced the number of degenerating neurons labeled with Fluoro-jade B in the brains of 5XFAD mice. The neuroprotective effect of NJK14047 was further confirmed by in vitro studies. Conclusion: Taken together, a selective p38α/β MAPKs inhibitor NJK14047 successfully showed therapeutic effects for AD in 5XFAD mice. Based on our data, p38 MAPKs inhibition is a potential strategy for AD therapy, suggesting NJK14047 as one of the promising candidates for AD therapeutics targeting p38 MAPKs. Keywords : Alzheimer’s disease, Amyloid-β, P38 mitogen-activated protein kinase, Kinase inhibitor, Microglia

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.

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