scholarly journals The Neuroprotective Effect of the Association of Aquaporin-4/Glutamate Transporter-1 against Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yu-Long Lan ◽  
Shuang Zou ◽  
Jian-Jiao Chen ◽  
Jie Zhao ◽  
Shao Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Ion Homeostasis ◽  
Water Channel ◽  
Glutamate Transporter ◽  
Aquaporin 4 ◽  
Normal Brain ◽  
Glutamate Transporter 1

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by memory loss and cognitive dysfunction. Aquaporin-4 (AQP4), which is primarily expressed in astrocytes, is the major water channel expressed in the central nervous system (CNS). This protein plays an important role in water and ion homeostasis in the normal brain and in various brain pathological conditions. Emerging evidence suggests that AQP4 deficiency impairs learning and memory and that this may be related to the expression of glutamate transporter-1 (GLT-1). Moreover, the colocalization of AQP4 and GLT-1 has long been studied in brain tissue; however, far less is known about the potential influence that the AQP4/GLT-1 complex may have on AD. Research on the functional interaction of AQP4 and GLT-1 has been demonstrated to be of great significance in the study of AD. Here, we review the interaction of AQP4 and GLT-1 in astrocytes, which might play a pivotal role in the regulation of distinct cellular responses that involve neuroprotection against AD. The association of AQP4 and GLT-1 could greatly supplement previous research regarding neuroprotection against AD.

scholarly journals Evaluation of the neuroprotective effect of taurine in Alzheimer’s disease using functional molecular imaging

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Se Jong Oh ◽  
Hae-June Lee ◽  
Ye Ji Jeong ◽  
Kyung Rok Nam ◽  
Kyung Jun Kang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Imaging ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Treatment Options ◽  
Brain Uptake ◽  
Positron Emission ◽  
Taurine Treatment

Abstract Alzheimer’s disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, but therapeutic treatment options are limited. Taurine has been reported to have neuroprotective properties against dementia, including AD. The present study aimed to investigate the treatment effect of taurine in AD mice by functional molecular imaging. To elucidate glutamate alterations by taurine, taurine was administered to 5xFAD transgenic mice from 2 months of age, known to apear amyloid deposition. Then, we performed glutamate positron emission tomography (PET) imaging studies for three groups (wild-type, AD, and taurine-treated AD, n = 5 in each group). As a result, brain uptake in the taurine-treated AD group was 31–40% higher than that in the AD group (cortex: 40%, p < 0.05; striatum: 32%, p < 0.01; hippocampus: 36%, p < 0.01; thalamus: 31%, p > 0.05) and 3–14% lower than that in the WT group (cortex: 10%, p > 0.05; striatum: 15%, p > 0.05; hippocampus: 14%, p > 0.05; thalamus: 3%, p > 0.05). However, we did not observe differences in Aβ pathology between the taurine-treated AD and AD groups in immunohistochemistry experiments. Our results reveal that although taurine treatment did not completely recover the glutamate system, it significantly increased metabolic glutamate receptor type 5 brain uptake. Therefore, taurine has therapeutic potential against AD.

scholarly journals L-Norvaline, a New Therapeutic Agent against Alzheimer’s disease

2018 ◽  
Author(s):  
Baruh Polis ◽  
Kolluru D Srikanth ◽  
Vyacheslav Gurevich ◽  
Hava Gil-Henn ◽  
Abraham O. Samson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Quantitative Polymerase Chain Reaction ◽  
Biological Pathways ◽  
Arginase Activity ◽  
Insidious Onset ◽  
Polymerase Chain

AbstractAlzheimer’s disease (AD) is a slowly progressive neurodegenerative disorder with an insidious onset. The disease is characterized by cognitive impairment and a distinct pathology with neuritic plaques and neurofibrillary tangles.Growing evidence highlights the role of arginase activity in the manifestation of AD. Upregulation of arginase was shown to contribute to endothelial dysfunction, atherosclerosis, diabetes, and neurodegeneration. Regulation of arginase activity appears to be a promising approach for interfering with the pathogenesis of AD and other metabolic disorders. Therefore, the enzyme represents a novel therapeutic target.Here, we administer an arginase inhibitor L-norvaline to a mouse model of AD. Then, we evaluate the neuroprotective effect of L-norvaline using immunohistochemistry, proteomics, and quantitative polymerase chain reaction assays. Finally, we identify the biological pathways activated by the treatment.Remarkably, we find that L-norvaline treatment reverses the cognitive decline in AD mice. We show the treatment is neuroprotective as indicated by reduced beta-amyloidosis, alleviated microgliosis, and TNFα transcription levels. Moreover, elevated levels of neuroplasticity related protein PSD-95 were detected in the hippocampi of mice treated with L-norvaline. Furthermore, we disclose several biological pathways, which are involved in cell survival and neuroplasticity and are activated by the treatment.Through these modes of action, L-norvaline has the potential to improve the symptoms of AD and even interfere with its pathogenesis. As such, L-norvaline is a promising neuroprotective molecule that might be tailored for the treatment of a range of neurodegenerative disorders.

scholarly journals The Neuroprotective Effect of L-Carnitine against Glyceraldehyde-Induced Metabolic Impairment: Possible Implications in Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2109
Author(s):  
Simona Magi ◽  
Alessandra Preziuso ◽  
Silvia Piccirillo ◽  
Francesca Giampieri ◽  
Danila Cianciosi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Survival ◽  
Mitochondrial Function ◽  
Cortical Neurons ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Mitochondrial Dynamics ◽  
Neuroprotective Effect ◽  
Memory Loss

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive regression and memory loss. Dysfunctions of both glucose metabolism and mitochondrial dynamics have been recognized as the main upstream events of the degenerative processes leading to AD. It has been recently found that correcting cell metabolism by providing alternative substrates can prevent neuronal injury by retaining mitochondrial function and reducing AD marker levels. Here, we induced an AD-like phenotype by using the glycolysis inhibitor glyceraldehyde (GA) and explored whether L-carnitine (4-N-trimethylamino-3-hydroxybutyric acid, LC) could mitigate neuronal damage, both in SH-SY5Y neuroblastoma cells and in rat primary cortical neurons. We have already reported that GA significantly modified AD marker levels; here we demonstrated that GA dramatically compromised cellular bioenergetic status, as revealed by glycolysis and oxygen consumption rate (OCR) evaluation. We found that LC ameliorated cell survival, improved OCR and ATP synthesis, prevented the loss of the mitochondrial membrane potential (Δψm) and reduced the formation of reactive oxygen species (ROS). Of note, the beneficial effect of LC did not rely on the glycolytic pathway rescue. Finally, we noticed that LC significantly reduced the increase in pTau levels induced by GA. Overall, these findings suggest that the use of LC can promote cell survival in the setting of the metabolic impairments commonly observed in AD. Our data suggest that LC may act by maintaining mitochondrial function and by reducing the pTau level.

scholarly journals Preparation of 4-Flexible Amino-2-Arylethenyl-Quinoline Derivatives as Multi-target Agents for the Treatment of Alzheimer’s Disease

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3100 ◽  
Author(s):  
Xiao-Qin Wang ◽  
Chu-Ping Zhao ◽  
Long-Cheng Zhong ◽  
De-Ling Zhu ◽  
De-Hao Mai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Aged People ◽  
Structure Activity ◽  
Aβ Aggregation ◽  
Aggregation Inhibition ◽  
Low Toxicity ◽  
Multifunctional Agents

Alzheimer’s disease (AD) is a complex and multifactorial neurodegenerative disorder of aged people. The development of multitarget-directed ligands (MTDLs) to act as multifunctional agents to treat this disease is the mainstream of current research. As a continuation of our previous studies, a series of 4-flexible amino-2-arylethenylquinoline derivatives as multi-target agents was efficiently synthesized and evaluated for the treatment of AD. Among these synthesized derivatives, some compounds exhibited strong self-induced Aβ1–42 aggregation inhibition and antioxidant activity. The structure-activity relationship was summarized, which confirmed that the introduction of a flexible amino group featuring a N,N-dimethylaminoalkylamino moiety at the 4-position increased the Aβ1–42 aggregation inhibition activity, with an inhibition ratio of 95.3% at 20 μM concentration. Compound 6b1, the optimal compound, was able to selectively chelate copper (II), and inhibit Cu2+-induced Aβ aggregation effectively. It also could disassemble the self-induced Aβ1–42 aggregation fibrils with a ratio of 64.3% at 20 μM concentration. Moreover, compound 6b1 showed low toxicity and a good neuroprotective effect against Aβ1–42-induced toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test indicated compound 6b1 significantly reversed scopolamine-induced memory deficit in mice. Taken together, these results suggested that compound 6b1 was a promising multi-target compound worthy of further study for AD.

scholarly journals Word-Embeddings and Grammar Features to Detect Language Disorders in Alzheimer’s Disease Patients

TecnoLógicas ◽  
2020 ◽  
Vol 23 (47) ◽  
pp. 63-75
Author(s):  
Juan S. Guerrero-Cristancho ◽  
Juan C. Vásquez-Correa ◽  
Juan R. Orozco-Arroyave
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Language Production ◽  
Neurodegenerative Disorder ◽  
Word Embedding ◽  
Normal Brain ◽  
Healthy Controls ◽  
Feature Sets ◽  
Early Fusion ◽  
Frequency Features

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that affects the language production and thinking capabilities of patients. The integrity of the brain is destroyed over time by interruptions in the interactions between neuron cells and associated cells required for normal brain functioning. AD comprises deterioration of the communicative skills, which is reflected in deficient speech that usually contains no coherent information, low density of ideas, and poor grammar. Additionally, patients exhibit difficulties to find appropriate words to structure sentences. Multiple ongoing studies aim to detect the disease considering the deterioration of language production in AD patients. Natural Language Processing techniques are employed to detect patterns that can be used to recognize the language impairments of patients. This paper covers advances in pattern recognition with the use of word-embedding and word-frequency features and a new approach with grammar features. We processed transcripts of 98 AD patients and 98 healthy controls in the Pitt Corpus of the Dementia-Bank database. A total of 1200 word-embedding features, 1408 Term Frequency—Inverse Document Frequency features, and 8 grammar features were extracted from the selected transcripts. Three models are proposed based on the separate extraction of such feature sets, and a fourth model is based on an early fusion strategy of the proposed feature sets. All the models were optimized following a Leave-One-Out cross validation strategy. Accuracies of up to 81.7 % were achieved using the early fusion of the three feature sets. Furthermore, we found that, with a small set of grammar features, accuracy values of up to 72.8 % were obtained. The results show that such features are suitable to effectively classify AD patients and healthy controls.

scholarly journals Behavioral, Neurochemical and Histological Changes in the Use of Low Doses of Naltrexone and Donepezil in the Treatment in Experimental Model of Alzheimer’s Disease by Induction of β-Amyloid1-42 in Rats

2019 ◽  
Vol 6 (1) ◽  
pp. 5-13
Author(s):  
Felipe Carmo De Moura ◽  
Marluy Kildary Fernandes Xavier ◽  
Francisca Eliane Lima Rodrigues ◽  
Marcos Fabio dos Santos Pinheiro ◽  
Erika Clemente Lima Machado ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Experimental Model ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Amyloid Peptide ◽  
Opioid Antagonist ◽  
Low Doses ◽  
Model Of Alzheimer’S Disease ◽  
Male Wistar Rats

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that promotes the involvement of memory-related functions, characterized by the presence of amyloid plaques formed by the β-amyloid peptide (Aβ), and hyperphosphorylated Tau protein neurofibrillary tangles. Evidence suggests that the use of low doses of Naltrexone, an opioid antagonist, possibly promotes a modulation of the immune system and consequent neuroprotective effect. The present study uses the animal model of induction with β-amyloid1-42 (Aβ1-42) to verify the behavioral, neurochemical and histological effects of the use of low doses of Naltrexone. Male wistar rats (250-300g) divided into five groups (N = 8) were used: Control, Sham, Aβ1-42 subdivided into three groups: treated with water, 05 mg Donepezil and 4.5 mg Naltrexone, orally during the 30-day period. Behavioral tests demonstrated the efficacy of induction to the experimental model with reduced memory of Aβ1-42-treated animals as well as reversal of damage in animals treated with Naltrexone. In the structural analysis, observed that the animals induced by Aβ1-42 treated with water alone presented alterations in the pyramidal forms of the hippocampal cells and that the animals treated with Naltrexone presented possibly a reversal of the neuronal damages. In conclusion, treatment with Naltrexone promoted a reversal in the memory impairment of rodents induced to the Alzheimer's model with Aβ1-42 in the behavioral and histological response.

scholarly journals A Novel Peroxidase Mimics and Ameliorates Alzheimer’s Disease-Related Pathology and Cognitive Decline in Mice

2018 ◽  
Vol 19 (11) ◽  
pp. 3304 ◽  
Author(s):  
Jia Xu ◽  
Kai Wang ◽  
Ye Yuan ◽  
Hui Li ◽  
Ruining Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Cognitive Decline ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Learning Ability ◽  
Human Neuroblastoma ◽  
Peroxidase Mimics

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the elderly, which is characterized by the accumulation of amyloid β (Aβ) plaques, oxidative stress, and neuronal loss. Therefore, clearing Aβ aggregates and reducing oxidative stress could be an effective therapeutic strategy for AD. Deuterohemin-AlaHisThrValGluLys (DhHP-6), a novel deuterohemin-containing peptide mimetic of the natural microperoxidase-11 (MP-11), shows higher antioxidant activity and stability compared to the natural microperoxidases. DhHP-6 possesses the ability of extending lifespan and alleviating paralysis in the Aβ1-42 transgenic Caenorhabditis elegans CL4176 model of AD, as shown in our previous study. Therefore, this study was aimed at exploring the neuroprotective effect of DhHP-6 in the APPswe/PSEN1dE9 transgenic mouse model of AD. DhHP-6 reduced the diameter and fiber structure of Aβ1-42 aggregation in vitro, as shown by dynamic light scattering and transmission electron microscope. DhHP-6 exerted its neuroprotective effect by inhibiting Aβ aggregation and plaque formation, and by reducing Aβ1-42 oligomers-induced neurotoxicity on HT22 (mouse hippocampal neuronal) and SH-SY5Y (human neuroblastoma) cells. In the AD mouse model, DhHP-6 significantly ameliorated cognitive decline and improved spatial learning ability in behavioral tests including the Morris water maze, Y-maze, novel object recognition, open field, and nest-building test. Moreover, DhHP-6 reduced the deposition of Aβ plaques in the cerebral cortex and hippocampus. More importantly, DhHP-6 restored the morphology of astrocytes and microglia, and significantly reduced the levels of pro-inflammatory cytokines. Our findings provide a basis for considering the non-toxic, peroxidase mimetic DhHP-6 as a new candidate drug against AD.

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