scholarly journals Therapeutic potential of nuclear receptor agonists in Alzheimer’s disease

2017 ◽  
Vol 58 (10) ◽  
pp. 1937-1949 ◽  
Author(s):  
Miguel Moutinho ◽  
Gary E. Landreth
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nuclear Receptor ◽  
Therapeutic Potential ◽  
Receptor Agonists

scholarly journals Omega-3 Fatty Acids Augment the Actions of Nuclear Receptor Agonists in a Mouse Model of Alzheimer's Disease

2015 ◽  
Vol 35 (24) ◽  
pp. 9173-9181 ◽  
Author(s):  
B. T. Casali ◽  
A. W. Corona ◽  
M. M. Mariani ◽  
J. C. Karlo ◽  
K. Ghosal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acids ◽  
Mouse Model ◽  
Nuclear Receptor ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Receptor Agonists ◽  
Model Of Alzheimer’S Disease

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

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.

The Therapeutic Potential of Purinergic Receptors in Alzheimer’s Disease and Promising Therapeutic Modulators

2020 ◽  
Vol 20 ◽  
Author(s):  
Lili Pan ◽  
Yu Ma ◽  
Yunchun Li ◽  
Haoxing Wu ◽  
Rui Huang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Purinergic Receptors ◽  
Therapeutic Potential ◽  
Purinergic Signaling ◽  
Memory Loss ◽  
Related Research ◽  
Central Nervous System Disorders ◽  
G Protein Coupled

Abstract:: Recent studies have proven that the purinergic signaling pathway plays a key role in neurotransmission and neuromodulation, and is involved in various neurodegenerative diseases and psychiatric disorders. With the characterization of the subtypes of receptors in purinergic signaling, i.e. the P1 (adenosine), P2X (ion channel) and P2Y (G protein-coupled), more attentions were paid to the pathophysiology and therapeutic potential of purinergic signaling in central nervous system disorders. Alzheimer’s disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. However, as drug development aimed to prevent or control AD follows a series of failures in recent years, more researchers focused on the neuroprotection-related mechanisms such as purinergic signaling in AD patients to find a potential cure. This article reviews the recent discoveries of purinergic signaling in AD, summaries the potential agents as modulators for the receptors of purinergic signaling in AD related research and treatments. Thus, our paper provided an insight for purinergic signaling in the development of anti-AD therapies.

Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease

2020 ◽  
Vol 17 (2) ◽  
pp. 141-157 ◽  
Author(s):  
Dubravka S. Strac ◽  
Marcela Konjevod ◽  
Matea N. Perkovic ◽  
Lucija Tudor ◽  
Gordana N. Erjavec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Therapeutic Potential ◽  
Relevant Literature ◽  
Comprehensive Overview ◽  
Brain Functions ◽  
Specific Effects ◽  
And Behavior

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease. Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease. Method: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles. Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications. Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.

scholarly journals A novel orally active HDAC6 inhibitor T-518 shows a therapeutic potential for Alzheimer’s disease and tauopathy in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomohiro Onishi ◽  
Ryouta Maeda ◽  
Michiko Terada ◽  
Sho Sato ◽  
Takahiro Fujii ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Drug Candidate ◽  
Histone Deacetylase 6 ◽  
Cellular Assays ◽  
Age Related ◽  
Acetylation State ◽  
Hdac6 Inhibitor ◽  
Orally Active

AbstractAccumulation of tau protein is a key pathology of age-related neurodegenerative diseases such as Alzheimer's disease and progressive supranuclear palsy. Those diseases are collectively termed tauopathies. Tau pathology is associated with axonal degeneration because tau binds to microtubules (MTs), a component of axon and regulates their stability. The acetylation state of MTs contributes to stability and histone deacetylase 6 (HDAC6) is a major regulator of MT acetylation status, suggesting that pharmacological HDAC6 inhibition could improve axonal function and may slow the progression of tauopathy. Here we characterize N-[(1R,2R)-2-{3-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-5-oxo-5H,6H,7H-pyrrolo[3,4-b]pyridin-6-yl}cyclohexyl]-2,2,3,3,3-pentafluoropropanamide (T-518), a novel, potent, highly selective HDAC6 inhibitor with clinically favorable pharmacodynamics. T-518 shows potent inhibitory activity against HDAC6 and superior selectivity over other HDACs compared with the known HDAC6 inhibitors in the enzyme and cellular assays. T-518 showed brain penetration in an oral dose and blocked HDAC6-dependent tubulin deacetylation at Lys40 in mouse hippocampus. A 2-week treatment restored impaired axonal transport and novel object recognition in the P301S tau Tg mouse, tauopathy model, while a 3-month treatment also decreased RIPA-insoluble tau accumulation. Pharmaceutical inhibition of HDAC6 is a potential therapeutic strategy for tauopathy, and T-518 is a particularly promising drug candidate.

Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer’s disease

2021 ◽  
Author(s):  
Ding-Yuan Tian ◽  
Yuan Cheng ◽  
Zhen-Qian Zhuang ◽  
Chen-Yang He ◽  
Qian-Guang Pan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Therapeutic Potential

Apoptotic Pathways and Alzheimer’s Disease: Probing Therapeutic Potential

2021 ◽  
Author(s):  
Vivek Kumar Sharma ◽  
Thakur Gurjeet Singh ◽  
Shareen Singh ◽  
Nikhil Garg ◽  
Sonia Dhiman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Apoptotic Pathways

Assessment of the therapeutic potential of hesperidin and proteomic resolution of diabetes-mediated neuronal fluctuations expediting Alzheimer’s disease

RSC Advances ◽  
2015 ◽  
Vol 5 (58) ◽  
pp. 46965-46980 ◽  
Author(s):  
Sapna Khowal ◽  
Malik M. A. Mustufa ◽  
Naveen K. Chaudhary ◽  
Samar Husain Naqvi ◽  
Suhel Parvez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Neuronal Damage ◽  
Early Stage ◽  
Type Iii

Alzheimer’s disease (AD) has been proposed as type III diabetes mellitus. Prognosis and early stage diagnosis of AD is essentially required in diabetes to avoid extensive irreversible neuronal damage.

Therapeutic potential of oxidant mechanisms in Alzheimer’s disease

2004 ◽  
Vol 4 (6) ◽  
pp. 995-1004 ◽  
Author(s):  
Paula I Moreira ◽  
Mark A Smith ◽  
Xiongwei Zhu ◽  
Maria S Santos ◽  
Catarina R Oliveira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential

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

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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