ISDN2014_0193: REMOVED: Beneficial effects of 17‐beta‐estradiol: A therapeutic potential drug for Alzheimer's disease

Multiple sclerosis and Alzheimer’s disease are two complex neurodegenerative diseases involving the immune system. So far, available treatments provide at best mild improvements to patients’ conditions. For decades now, a new set of molecules have been used to modulate and regulate the innate immunity in these pathologies. Most studies have been carried out in rodents and some of them have reported tremendous beneficial effects on the disease course. The modulation of innate immune cells is of great interest since it provides new hope for patients. In this review, we will briefly overview the therapeutic potential of some molecules and receptors in multiple sclerosis and Alzheimer’s disease and how they could be used to exploit new therapeutic avenues.

Download Full-text

Curcuminoids and Novel Opportunities for the Treatment of Alzheimer's Disease: Which Molecules are Actually Effective?

Current Molecular Pharmacology ◽

10.2174/1874467211666181012150847 ◽

2019 ◽

Vol 12 (1) ◽

pp. 12-26 ◽

Cited By ~ 3

Author(s):

Alexander V. Zholos ◽

Olesia F. Moroz ◽

Maksim V. Storozhuk

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Animal Models ◽

Therapeutic Potential ◽

Relevant Literature ◽

Preclinical Studies ◽

In Vitro Experiments ◽

Beneficial Effects

Background:Millions of people worldwide are suffering from Alzheimer's disease (AD), and there are only symptomatic treatments available for this disease. Thus, there is a great need to identify drugs capable of arresting or reversing AD. Constituents of the spice turmeric, in particular, curcuminoids, seem to be very promising, as evident from in vitro experiments and tests using animal models of AD. However, most of the clinical trials did not reveal any beneficial effects of curcuminoids in the treatment of AD. These controversies, including conflicting results of clinical trials, are thought to be related to bioavailability of curcuminoids, which is low unless it is enhanced by developing a special formulation. However, there is growing evidence suggesting that other reasons may be of even greater importance, but these avenues are less explored.Objective:Review relevant literature, and analyze potential reasons for the controversial results.Methodology:Recent in vitro and preclinical studies; clinical trials (without a limiting period) were searched in PubMed and Google Scholar.Results:While recent in vitro and preclinical studies confirm the therapeutic potential of curcuminoids in the treatment of AD and cognitive dysfunctions, results of corresponding clinical trials remain rather controversial.Conclusion:The controversial results obtained in the clinical trials may be in part due to particularities of the curcuminoid formulations other than bioavailability. Namely, it seems likely that the various formulations differ in terms of their minor turmeric constituent(s). We hypothesize that these distinctions may be of key importance for efficacy of the particular formulation in clinical trials. A testable approach addressing this hypothesis is suggested.

Download Full-text

Modulating disease-relevant tau oligomeric strains by small molecules

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.014630 ◽

2020 ◽

Vol 295 (44) ◽

pp. 14807-14825 ◽

Cited By ~ 1

Author(s):

Filippa Lo Cascio ◽

Stephanie Garcia ◽

Mauro Montalbano ◽

Nicha Puangmalai ◽

Salome McAllen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Diseases ◽

Therapeutic Potential ◽

Lewy Bodies ◽

Aggregation State ◽

Beneficial Effects ◽

Tau Oligomers ◽

Curcumin Derivatives ◽

Aggregation Pattern

The pathological aggregation of tau plays an important role in Alzheimer's disease and many other related neurodegenerative diseases, collectively referred to as tauopathies. Recent evidence has demonstrated that tau oligomers, small and soluble prefibrillar aggregates, are highly toxic due to their strong ability to seed tau misfolding and propagate the pathology seen across different neurodegenerative diseases. We previously showed that novel curcumin derivatives affect preformed tau oligomer aggregation pathways by promoting the formation of more aggregated and nontoxic tau aggregates. To further investigate their therapeutic potential, we have extended our studies o disease-relevant brain-derived tau oligomers (BDTOs). Herein, using well-characterized BDTOs, isolated from brain tissues of different tauopathies, including Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies, we found that curcumin derivatives modulate the aggregation state of BDTOs by reshaping them and rescue neurons from BDTO-associated toxicity. Interestingly, compound CL3 showed an effect on the aggregation pattern of BDTOs from different tauopathies, resulting in the formation of less neurotoxic larger tau aggregates with decreased hydrophobicity and seeding propensity. Our results lay the groundwork for potential investigations of the efficacy and beneficial effects of CL3 and other promising compounds for the treatment of tauopathies. Furthermore, CL3 may aid in the development of tau imaging agent for the detection of tau oligomeric strains and differential diagnosis of the tauopathies, thus enabling earlier interventions.

Download Full-text

Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease β Secretase, BACE1

Marine Drugs ◽

10.3390/md19040203 ◽

2021 ◽

Vol 19 (4) ◽

pp. 203

Author(s):

Courtney J. Mycroft-West ◽

Anthony J. Devlin ◽

Lynsay C. Cooper ◽

Scott E. Guimond ◽

Patricia Procter ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Litopenaeus Vannamei ◽

Therapeutic Potential ◽

Anticoagulant Activity ◽

Amyloid Peptide ◽

Drug Candidates ◽

Beneficial Effects ◽

Target Drug ◽

And Oxidative Stress

Only palliative therapeutic options exist for the treatment of Alzheimer’s Disease; no new successful drug candidates have been developed in over 15 years. The widely used clinical anticoagulant heparin has been reported to exert beneficial effects through multiple pathophysiological pathways involved in the aetiology of Alzheimer’s Disease, for example, amyloid peptide production and clearance, tau phosphorylation, inflammation and oxidative stress. Despite the therapeutic potential of heparin as a multi-target drug for Alzheimer’s disease, the repurposing of pharmaceutical heparin is proscribed owing to the potent anticoagulant activity of this drug. Here, a heterogenous non-anticoagulant glycosaminoglycan extract, obtained from the shrimp Litopenaeus vannamei, was found to inhibit the key neuronal β-secretase, BACE1, displaying a more favorable therapeutic ratio compared to pharmaceutical heparin when anticoagulant activity is considered.

Download Full-text

Mechanisms for the protective effects of 17-beta-estradiol: a therapeutic potential drug for Alzheimer’s disease

Cytotherapy ◽

10.1016/j.jcyt.2013.01.129 ◽

2013 ◽

Vol 15 (4) ◽

pp. S34 ◽

Cited By ~ 1

Author(s):

P. Kumar ◽

R. Kale ◽

N. Baquer

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Therapeutic Potential ◽

Protective Effects ◽

Potential Drug

Download Full-text

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.

Download Full-text