scholarly journals miR-485-5p alleviates Alzheimer’s disease progression by targeting PACS1

2021 ◽  
Vol 12 (1) ◽  
pp. 335-345
Author(s):  
Chuan He ◽  
Caixia Su ◽  
Wentong Zhang ◽  
Qi Wan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Function ◽  
Neurological Diseases ◽  
Flow Cytometric Analysis ◽  
Immunofluorescent Staining ◽  
Luciferase Reporter ◽  
Morris Water Maze Test ◽  
Flow Cytometric ◽  
Maze Test

Abstract Alzheimer’s disease (AD) is a common dementia and a heterogeneous disease. Previous research has validated that microRNAs (miRNAs) are pivotal regulators in the initiation and development of tremendous diseases including AD. MicroRNA-485-5p (miR-485-5p) was reported to be an important participant implicated in several neurological diseases, but its role in AD still needs to be further investigated. In this research, we explored the biological function of miR-485-5p in AD. RT-qPCR revealed that miR-485-5p expression was downregulated in the hippocampus of APP/PS1 mice. Additionally, miR-485-5p overexpression facilitated the learning and memory capabilities of APP/PS1 mice according to Morris water maze test, fear conditioning test, and immunofluorescent staining. Moreover, CCK-8 assay, flow cytometric analysis, and western blot analysis suggested that miR-485-5p overexpression promoted pericyte viability and prohibited pericyte apoptosis in APP/PS1 mice. Mechanistically, miR-485-5p directly targeted PACS1 in pericytes, as shown in a luciferase reporter assay. In rescue assays, PACS1 overexpression countervailed the effect of miR-485-5p overexpression on pericyte viability and apoptosis. In conclusion, miR-485-5p ameliorates AD progression by targeting PACS1.

scholarly journals Musical Electroacupuncture May Be a Better Choice than Electroacupuncture in a Mouse Model of Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jing Jiang ◽  
Gang Liu ◽  
Suhua Shi ◽  
Zhigang Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Frontal Lobe ◽  
Morris Water Maze ◽  
Water Maze ◽  
Morris Water Maze Test ◽  
Maze Test ◽  
Model Of Alzheimer’S Disease ◽  
Samp8 Mice

Objectives. To compare musical electroacupuncture and electroacupuncture in a mouse model of Alzheimer’s disease.Methods. In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an Alzheimer’s disease animal model. In the normal control paradigm, 7.5-month-old male SAMR1 mice were used as the blank control group (N group). After 15 days of treatment, using Morris water maze test, micro-PET, and immunohistochemistry, the differences among the musical electroacupuncture (MEA), electroacupuncture (EA), Alzheimer’s disease (AD), and normal (N) groups were assessed.Results. The Morris water maze test, micro-PET, and immunohistochemistry revealed that MEA and EA therapies could improve spatial learning and memory ability, glucose metabolism level in the brain, and Aβamyloid content in the frontal lobe, compared with the AD group (P<0.05). Moreover, MEA therapy performed better than EA treatment in decreasing amyloid-beta levels in the frontal lobe of mice with AD.Conclusion. MEA therapy may be superior to EA in treating Alzheimer’s disease as demonstrated in SAMP8 mice.

scholarly journals EVALUATION OF ANTI-ALZHEIMER ACTIVITY OF ETHANOLIC AND METHANOLIC EXTRACTS OF POLYGONUM GLABRUM AGAINST ALUMINUM CHLORIDE-INDUCED ALZHEIMER’S IN EXPERIMENTAL RATS

2021 ◽  
pp. 118-125
Author(s):  
SUNEESHA Y ◽  
VINAY KUMAR T
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Aluminum Chloride ◽  
Methanolic Extract ◽  
Ethanolic Extract ◽  
Morris Water Maze Test ◽  
Methanolic Extracts ◽  
Maze Test ◽  
Behavioral Parameters ◽  
Acetylcholinesterase Enzyme

Objective: The current study aimed at the investigation of the effectiveness of ethanolic and methanolic extract of Polygonum glabrum in aluminum chloride-induced Alzheimer’s disease in experimental rats. Methods: The behavioral parameters evaluated by following methods such as Morris water maze test, radial arm maze test, and active avoidance test. Biochemical parameters were also estimated such as acetylcholine and acetylcholine esterase. Results: Polygonum glabrum extract was instituted to be neuroprotective against AlCl3-induced toxicity. Enhanced learning and memory were allied to the ingestion of extract in rats. Al overload, acetylcholinesterase enzyme hyperactivity is responsible for Alzheimer’s disease which is neutralized or reduced with treatment of extract, which might be due to the synergistic action of its active constituents. Ethanolic extract was shown slightly higher efficacy as compared to methanolic extract. Conclusion: Based on these current findings, it is suggested that lowering Aβ is an unproven strategy, and it may be time to refocus on other targets for the treatment of this disease, including pathological forms of tau.

Overexpression of miR-26a-5p Suppresses Tau Phosphorylation and Aβ Accumulation in the Alzheimer’s Disease Mice by Targeting DYRK1A

2020 ◽  
Vol 17 (3) ◽  
pp. 241-248 ◽  
Author(s):  
Yanni Liu ◽  
Lin Wang ◽  
Fuheng Xie ◽  
Xiao Wang ◽  
Yuanyuan Hou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Development ◽  
Tau Phosphorylation ◽  
Luciferase Reporter ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
Latency Time ◽  
Underlying Mechanisms

Objective: It is reported that miR-26a-5p could regulate neuronal development, but its underlying mechanisms in Alzheimer’s disease (AD) progression is unclear. Methods: APP (swe)/PS1 (ΔE9) transgenic mice served as AD mice. Morris water maze test was used to measure the spatial learning and memory ability of mice. The expressions of miR-26a-5p, DYRK1A, phosphorylated-Tau, Aβ40, and Aβ42 were detected. The relationship between miR- 26a-5p and DYRK1A was explored using dual luciferase reporter assay. The effects of miR-26a- 5p on AD mice was determined. Results: AD mice walked a lot of wrong ways to find the platform area and the latency time to reach the platform was longer. There was low expression of MiR-26a-5p in AD mice. Overexpression of miR-26a-5p inhibited Tau phosphorylation and Aβ accumulation. MiR-26a-5p negatively regulated DYRK1A via targeting its 3’UTR. In vivo, increased miR-26a-5p down-regulated Aβ40, Aβ42, p-APP and p-Tau levels in AD mice through decreasing DYRK1A. Meanwhile, the swimming path and the latency time, to reach the platform, was shorten after enhancing miR-26a-5p expression. Conclusion: Overexpression of miR-26a-5p could repress Tau phosphorylation and Aβ accumulation via down-regulating DYRK1A level in AD mice.

scholarly journals Effect of Piper betel leaf extract on learning and memory in Aluminium chloride induced Alzheimer’s disease in Wistar rats

2019 ◽  
Vol 12 (3) ◽  
pp. 1425-1431
Author(s):  
Shreeraksha Upadhyaya ◽  
Shivaprakash Gangachannaiah ◽  
Pallavi Lakshmi Chandrashekar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Wistar Rats ◽  
Treated Group ◽  
Aluminium Chloride ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Betel Leaf ◽  
Maze Test ◽  
Piper Betel Leaf

Alzheimer's disease is a common neurological disorder affecting a significant proportion of the elderly population.There are only a few drugs which can be used safely to treat it. We sought to investigate for the first time Piper betel leaf, a postmeal mouth freshener for its potential use in Alzheimer's disease. Five groups of male Wistar rats with six rats in each group aged 10-12 weeks were used. The control group received the distilled water, aluminium chloride (AlCl3) group was treated with AlCl3, the standard group was treated with rivastigmine with AlCl3, and the two test groups received piper betel leaf extract (PBE) at doses of 400mg/kg and 500mg/kg body weight with AlCl3. AlCl3 was administered orally for 42 days in all the treated groups. Memory and learning were evaluated by Morris water maze test and Passive avoidance test.The results of the Morris water maze test showed reduced mean escape latency period in all the groups on trial day three (P≤0.05) and on trial day four (P ≤0.01) compared to AlCl3 group. The retention of spatial memory by probe trial showed that PBE and rivastigmine treated group spent more time in the target (platform) quadrant when compared to AlCl3 group (P≤0.01). The passive avoidance test showed a significant increase in step through latency in standard and test groups compared to the AlCl3 treated group. The weight of the rats treated with AlCl3 and PBE was reduced at the end of the treatment period while increased in standard and control group. The study shows the beneficial effects of Piper betel leaves in Alzheimer’s disease by significantly improving the learning and memory functions in rats.

scholarly journals High Methionine Diet-Induced Alzheimer’s Disease like Symptoms Are Accompanied by 5-Methylcytosine Elevated Levels in the Brain

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Tingting Pi ◽  
Shenjiao Wei ◽  
Yongxuan Jiang ◽  
Jing-Shan Shi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Food Intake ◽  
Amyloid Β ◽  
The Body ◽  
Morris Water Maze Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ability Test ◽  
Maze Test ◽  
Related Proteins

Background. Excessive or insufficient intake of methionine (Met) causes neuronal dysfunction, neurodegeneration, cerebrovascular dysfunction, vascular leakage, and short-term memory loss, which result in the occurrence of Alzheimer’s disease- (AD-) like symptoms. Objective. To determine the relationship between high methionine diets (HMD) induced AD-like symptoms and 5-methylcytosine (5-mC) level. Methods. C57BL/6J mice were randomly divided into two groups: the control group (Maintain diets) and the model group (2% HMD). Mice were fed with 2% HMD for 9 weeks. Animals were weighed and food intake was recorded weekly. Open field test, nesting ability test, Y maze test, new object recognition test, and Morris water maze test were used to detect the motor, learning, and memory ability. Hematoxylin-eosin (HE) staining was used to observe the damage of cells in hippocampus and cortex. Immunofluorescence (IF) staining was used to detect the expression and distribution of amyloid-β 1-40 (Aβ1-40), amyloid-β 1-42 (Aβ1-42), and 5-methylcytosine (5-mC) in hippocampus and cortex. Western blotting (WB) was used to determine the expression of Aβ and DNA methyltransferases- (DNMTs-) related proteins in the cortex. Enzyme-linked immunosorbent assay (ELISA) was performed to detect homocysteine (Hcy) level (ELISA). Results. Feeding of HMD decreased the body weight and food intake of mice. Behavioral testing revealed that HMD caused learning, memory, and motor ability impairment in the mice. HE staining results showed that HMD feeding caused damage of hippocampal and cortical neurons, along with disordered cell arrangement, and loss of neurons. Furthermore, HMD increased the contents of Aβ1-40, Aβ1-42, and 5-mC in the hippocampus and cortex. WB results showed that HMD increased the expression of Aβ production-related proteins, such as amyloid precursor protein (APP) and beta-secretase 1 (BACE1), and decreased the expression of Aβ metabolism-related protein in the cortex, including insulin-degrading enzyme (IDE) and neprilysin (NEP). Additionally, the decreased expression of DNA methyltransferase1 (DNMT1) was observed in HMD-treated mice, but there was no significant change of DNMT3a level. ELISA results showed that HMD increased the levels of Hcy in serum. Conclusion. Our result suggested that the HMD can cause neurotoxicity, leading to AD-like symptoms in mice, which may be related to 5-mC elevated.

Alzheimer’s Disease Targeted Nano-Based Drug Delivery Systems

2020 ◽  
Vol 21 (7) ◽  
pp. 628-646
Author(s):  
Gülcem Altinoglu ◽  
Terin Adali
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Neurological Diseases ◽  
Sustained Drug Release ◽  
Physiochemical Properties ◽  
Conventional Drug ◽  
Health Care Burden ◽  
The Central Nervous System ◽  
Effective Drugs

Alzheimer’s disease (AD) is the most common neurodegenerative disease, and is part of a massive and growing health care burden that is destroying the cognitive function of more than 50 million individuals worldwide. Today, therapeutic options are limited to approaches with mild symptomatic benefits. The failure in developing effective drugs is attributed to, but not limited to the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. In addition, targeted drug delivery to the central nervous system (CNS), for the diagnosis and therapy of neurological diseases like AD, is restricted by the challenges posed by blood-brain interfaces surrounding the CNS, limiting the bioavailability of therapeutics. Research done over the last decade has focused on developing new strategies to overcome these limitations and successfully deliver drugs to the CNS. Nanoparticles, that are capable of encapsulating drugs with sustained drug release profiles and adjustable physiochemical properties, can cross the protective barriers surrounding the CNS. Thus, nanotechnology offers new hope for AD treatment as a strong alternative to conventional drug delivery mechanisms. In this review, the potential application of nanoparticle based approaches in Alzheimer’s disease and their implications in therapy is discussed.

scholarly journals Astrocytic transporters in Alzheimer's disease

2017 ◽  
Vol 474 (3) ◽  
pp. 333-355 ◽  
Author(s):  
Chris Ugbode ◽  
Yuhan Hu ◽  
Benjamin Whalley ◽  
Chris Peers ◽  
Marcus Rattray ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Neurological Diseases ◽  
Current Evidence ◽  
Specific Targeting ◽  
Disease Modifying Therapies ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
And Function

Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture. Therefore, specific targeting of individual transporter families has the potential to suppress neurodegeneration, a characteristic hallmark of AD. A small number of the 400 transporter superfamilies are expressed in astrocytes, with evidence highlighting a fraction of these are implicated in AD. Here, we review the current evidence for six astrocytic transporter subfamilies involved in AD, as reported in both animal and human studies. This review confirms that astrocytes are indeed a viable target, highlights the complexities of studying astrocytes and provides future directives to exploit the potential of astrocytes in tackling AD.

Caracole as a Potential Neuroprotective Agent for Neurological Diseases: A Systematic

2021 ◽  
Vol 20 ◽  
Author(s):  
Mohammad Zamanian ◽  
Małgorzata Kujawska ◽  
Marjan Nikbakht Zadeh ◽  
Amin Hassanshahi ◽  
Soudeh Ramezanpour ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Parkinson's Disease ◽  
Brain Injury ◽  
Neurological Diseases ◽  
Antioxidant Systems ◽  
Neuroprotective Agent ◽  
The Impact

Background & objective: Neurological diseases are becoming a significant problem worldwide, with the elderly at a higher risk of being affected. Several researchers have investigated the neuroprotective effects of Carvacrol (CAR) (5-isopropyl-2-methyl phenol). This review systematically surveys the existing literature on the impact of CAR when used as a neuroprotective agent in neurological diseases. Methods: The systematic review involved English articles published in the last ten years obtained from PubMed, Google Scholar, and Scopus databases. The following descriptors were used to search the literature: “Carvacrol” [Title] AND “neuroprotective (neuroprotection)” [Title] OR “stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, seizure, epilepsy [Title]. Results: : A total of 208 articles were retrieved during the search process, but only 20 studies met the eligibility criteria and were included for review. A total of 20 articles were identified, in which the efficacy of CAR was described in experimental models of stroke, traumatic brain injury, Parkinson’s disease, Alzheimer’s disease, , epilepsy, and seizure, through motor deficits improvements in neurochemical activity, especially antioxidant systems, reducing inflammation, oxidative stress and apoptosis as well as inhibition of TRPC1 and TRPM7. Conclusion : The data presented in this study support the beneficial impact of CAR on behavioural and neurochemical deficits. CAR benefits accrue because of its anti-apoptotic, antioxidant, and anti-inflammatory properties. Therefore, CAR has emerged as an alternative treatment for neurological disorders based on its properties.

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