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

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.

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Neuroprotective Effects of Ellagic Acid in Alzheimer's Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential

Current Pharmaceutical Design ◽

10.2174/1381612826666201112144006 ◽

2020 ◽

Vol 26 ◽

Author(s):

Nimra Javaid ◽

Muhammad Ajmal Shah ◽

Azhar Rasul ◽

Zunera Chauhdary ◽

Uzma Saleem ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Ellagic Acid ◽

Molecular Mechanisms ◽

Neurodegenerative Disorder ◽

Therapeutic Potential ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Acetylcholinesterase Activity ◽

Neuroprotective Effects

: Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead towards neuronal cell death. Alzheimer’s disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset yet later on it worsens. The documented evidence of AD neuropathology manifested the neuro-inflammation, increased reactive oxygen, nitrogen species and decreased antioxidant protective process; mitochondrial dysfunction as well as increased level of acetylcholinesterase activity. Moreover, enhanced action of proteins leads towards neural apoptosis which have a vital role in the degeneration of neurons. The inability of commercial therapeutic options to treat AD with targeting single mechanism leads the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid, latest studies expressed that ellagic acid can initiate the numerous cell signaling transmission and decrease the progression of disorders, involved in the degeneration of neurons. The influential property of ellagic acid to protect the neurons in neurodegenerative disorders is due to its antioxidant effect, iron chelating and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mode of action of ellagic acid against neurodegeneration.

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Neuroprotective Activity of the Methanolic Extract of Indigofera aspalathoides against Scopalamine induced Alzheimer's Disease in Experimental Rats

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00898 ◽

2021 ◽

pp. 5163-5168

Author(s):

Rajaram C. ◽

S. Nelson Kumar ◽

S. S. Sheeba Tabassum ◽

Manohar R. ◽

Sumanjali C.

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Traditional Medicine ◽

Methanolic Extract ◽

Therapeutic Potential ◽

Neuroprotective Effect ◽

Neuroprotective Activity ◽

Control Group ◽

Histological Structure ◽

Anticancer Activities

The plant Indigofera aspalathoides is a traditional medicine with tremendous therapeutic potential which finds it use in treatment of various ailments such as antibacterial, antioxidant, anti-inflammatory, antidiabetic, and anticancer activities. There are no reports that related to the use of this plant in treating patients with Alzheimer’s disease (AD). Hence present study was aimed to scientifically evaluate the neuroprotective effect of the methanolic extract of Indigofera aspalathoides against scopalamine induced Alzheimer’s disease in experimental rats using behavioral tests like elevated plus maze, Y-maze, and rota-rod tests. In addition to this, biochemical evaluation for acetylcholinesterase activity and histopathological evaluation of brain were done. The results suggests that methanolic extract Indigofera aspalathoides (200mg/kg B.wt and 400mg/kg B.wt) used in this study shows significant improvement of various behavioral parameters like locomotion, anxiety, memory, motor integrity and coordination etc when compared to control group. MEIA inhibited brain AChE enzyme, thereby elevating Ach concentration in brain homogenate and ultimately improved memory of rats. Further, more or less normal histological structure of the hippocampus and all amyloid plaques and neurofibrillary tangles that are formed under the influence of scopolamine disappeared in the rats pretreated with MEIA (200mg/kg B.wt and 400mg/kg B.wt). It can be concluded that our results strongly support the anti-Alzheimer’s potential of the methanolic extract of the plant I.aspalathoides and its use in traditional medicine.

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AADVAC1, AN ACTIVE IMMUNOTHERAPY FOR ALZHEIMER’S DISEASE AND NON ALZHEIMER TAUOPATHIES: AN OVERVIEW OF PRECLINICAL AND CLINICAL DEVELOPMENT

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2018.45 ◽

2018 ◽

pp. 1-7

Author(s):

P. Novak ◽

N. Zilka ◽

M. Zilkova ◽

B. Kovacech ◽

R. Skrabana ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Tau Protein ◽

Neurodegenerative Disorder ◽

Therapeutic Potential ◽

Phase 1 ◽

Primary Progressive Aphasia ◽

Tau Proteins ◽

Active Immunotherapy ◽

Tau Pathology

Neurofibrillary tau protein pathology is closely associated with the progression and phenotype of cognitive decline in Alzheimer’s disease and other tauopathies, and a high-priority target for disease-modifying therapies. Herein, we provide an overview of the development of AADvac1, an active immunotherapy against tau pathology, and tau epitopes that are potential targets for immunotherapy. The vaccine leads to the production of antibodies that target conformational epitopes in the microtubule-binding region of tau, with the aim to prevent tau aggregation and spreading of pathology, and promote tau clearance. The therapeutic potential of the vaccine was evaluated in transgenic rats and mice expressing truncated, non mutant tau protein, which faithfully replicate of human tau pathology. Treatment with AADvac1 resulted in reduction of neurofibrillary pathology and insoluble tau in their brains, and amelioration of their deleterious phenotype. The vaccine was highly immunogenic in humans, inducing production of IgG antibodies against the tau peptide in 29/30 treated elderly patients with mild-to-moderate Alzheimer’s. These antibodies were able to recognise insoluble tau proteins in Alzheimer patients’ brains. Treatment with AADvac1 proved to be remarkably safe, with injection site reactions being the only adverse event tied to treatment. AADvac1 is currently being investigated in a phase 2 study in Alzheimer’s disease, and a phase 1 study in non-fluent primary progressive aphasia, a neurodegenerative disorder with a high tau pathology component.

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Mesenchymal Stem Cell-Derived Extracellular Vesicle-Based Therapy for Alzheimer’s Disease: Progress and Opportunity

Membranes ◽

10.3390/membranes11100796 ◽

2021 ◽

Vol 11 (10) ◽

pp. 796

Author(s):

Yi-An Chen ◽

Cheng-Hsiu Lu ◽

Chien-Chih Ke ◽

Ren-Shyan Liu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Therapeutic Potential ◽

Extracellular Vesicle ◽

Synaptic Loss ◽

Molecular Machinery ◽

And Function ◽

Preclinical And Clinical Studies ◽

Ad Therapy

Alzheimer’s disease (AD), as a neurodegenerative disorder, is characterized by mass neuronal and synaptic loss and, currently, there are no successful curative therapies. Extracellular vesicles (EVs) are an emerging approach to intercellular communication via transferring cellular materials such as proteins, lipids, mRNAs, and miRNAs from parental cells to recipient cells, leading to the reprogramming of the molecular machinery. Numerous studies have suggested the therapeutic potential of EVs derived from mesenchymal stem cells (MSCs) in the treatment of AD, based on the neuroprotective, regenerative and immunomodulatory effects as effective as MSCs. In this review, we focus on the biology and function of EVs, the potential of MSC-derived EVs for AD therapy in preclinical and clinical studies, as well as the potent mechanisms of MSC-derived EVs actions. Finally, we highlight the modification strategies and diagnosis utilities in order to make advance in this field.

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Molecular Imaging in Alzheimer’s Disease

European Neurological Review ◽

10.17925/enr.2011.06.01.16 ◽

2011 ◽

Vol 6 (1) ◽

pp. 16

Author(s):

Karl Herholz ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Imaging ◽

Clinical Symptoms ◽

Accurate Method ◽

Imaging Biomarker ◽

Pet Tracer ◽

Specificity And Sensitivity ◽

Positron Emission ◽

Dementia Research

The most sensitive and accurate method for molecular imaging in human Alzheimer’s disease (AD) is positron emission tomography (PET). The most widely available PET tracer, which is also used in clinical oncology, is 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG is an imaging biomarker for early and differential diagnosis of AD. Even higher molecular specificity and sensitivity for detection of AD before dementia onset is provided by high-affinity ligands for fibrillary amyloid. 11C-Pittsburgh Compound B is widely being used in research laboratories, while new 18F-labelled ligands are currently undergoing formal clinical trials as amyloid imaging agents and are expected to become commercially available for clinical use in the near future. A large variety of tracers is being developed and used in dementia research for activated microglia and multiple neurotransmitter systems to study disease pathophysiology, biological correlates of clinical symptoms and new possibilities for treatment. Current studies in humans are investigating cholinergic, serotonergic and dopaminergic neurotransmission.

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Effect of plant extracts on Alzheimer’s disease: An insight into therapeutic avenues

Journal of Neurosciences in Rural Practice ◽

10.4103/0976-3147.80102 ◽

2011 ◽

Vol 02 (01) ◽

pp. 056-061 ◽

Cited By ~ 27

Author(s):

M Obulesu ◽

Dowlathabad Muralidhara Rao

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Treatment Options ◽

Ache Inhibition ◽

Melissa Officinalis ◽

Lemon Balm ◽

Aggregation Effect ◽

Insight Into ◽

Maidenhair Tree

ABSTRACTAlzheimer’s disease (AD) is a devastative neurodegenerative disorder which needs adequate studies on effective treatment options. The extracts of plants and their effect on the amelioration of AD symptoms have been extensively studied. This paper summarizes the mechanisms like acetylcholinesterase (AChE) inhibition, modifi cation of monoamines, antiamyloid aggregation effect, and antioxidant activity which are actively entailed in the process of amelioration of AD symptoms. These effects are induced by extracts of a few plants of different origin like Yizhi Jiannao, Moringaoleifera (Drumstick tree), Ginkgo Biloba (Ginkgo/Maidenhair tree), Cassia obtisufolia (Sicklepod), Desmodium gangeticum (Sal Leaved Desmodium), Melissa officinalis (Lemon Balm), and Salvia officinalis (Garden sage, common sage).

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Molecular Imaging and Magnetic Resonance Imaging in Early Diagnosis of Alzheimer's Disease

The Neuroradiology Journal ◽

10.1177/197140090802100603 ◽

2008 ◽

Vol 21 (6) ◽

pp. 755-771

Author(s):

O. Schillaci ◽

L. Travascio ◽

C. Bruni ◽

G. Bazzocchi ◽

A. Testa ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Imaging ◽

Magnetic Resonance ◽

Early Diagnosis ◽

Neurodegenerative Disorder ◽

The Elderly ◽

Resonance Imaging ◽

New Techniques ◽

Molecular Imaging Agents

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in the elderly. Magnetic resonance (MR) or computed tomography (CT) imaging is recommended for routine evaluation of dementias. The development of molecular imaging agents and the new techniques of MR for AD are critically important for early diagnosis, neuropathogenesis studies and assessing treatment efficacy in AD. Neuroimaging using nuclear medicine techniques such as SPECT, PET and MR spectroscopy has the potential to characterize the biomarkers for Alzheimer's disease. The present review summarizes the results of radionuclide imaging and MR imaging in AD.

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

Neural Plasticity ◽

10.1155/2016/4626593 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 11

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.

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

10.1101/491480 ◽

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.

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A Primer on the Evolution of Aducanumab: The First Antibody Approved for Treatment of Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-215065 ◽

2021 ◽

pp. 1-16

Author(s):

Sanchari Mukhopadhyay ◽

Debanjan Banerjee

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Monoclonal Antibody ◽

Cholesterol Metabolism ◽

Neurodegenerative Disorder ◽

Treatment Options ◽

Surrogate Marker ◽

Amyloid Β ◽

Clinical Endpoints ◽

Definition Of

Alzheimer’s disease (AD) is the most common form of dementia with global burden projected to triple by 2050. It incurs significant biopsychosocial burden worldwide with limited treatment options. Aducanumab is the first monoclonal antibody recently approved by the US-FDA for mild AD through the accelerated approval pathway. It is the first molecule to be approved for AD since 2003 and carries with it a therapeutic promise for the future. As the definition of AD has evolved from a pathological entity to a clinic-biological construct over the years, the amyloid-β (Aβ) pathway has been increasingly implicated in its pathogenesis. The approval of Aducanumab is based on reduction of the Aβ load in the brain, which forms a surrogate marker for this pathway. The research populace has, however, been globally divided by skepticism and hope regarding this approval. Failure to meet clinical endpoints in the trials, alleged transparency issues, cost-effectiveness, potential adverse effects, need for regular monitoring, and critique of ‘amyloid cascade hypothesis’ itself are the main caveats concerning the antibody. With this controversy in background, this paper critically looks at antibody research in AD therapeutics, evidence, and evolution of Aducanumab as a drug and the potential clinical implications of its use in future. While the efficacy of this monoclonal antibody in AD stands as a test of time, based on the growing evidence it is vital to rethink and explore alternate pathways of pathogenesis (oxidate stress, neuroinflammation, cholesterol metabolism, vascular factors, etc.) as possible therapeutic targets that may help elucidate the enigma of this complex yet progressive and debilitating neurodegenerative disorder.

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