Beneficial Effects of Fingolimod in Alzheimer’s Disease: Molecular Mechanisms and Therapeutic Potential

: 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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Functional Foods: An Approach to Modulate Molecular Mechanisms of Alzheimer’s Disease

Cells ◽

10.3390/cells9112347 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2347

Author(s):

Anna Atlante ◽

Giuseppina Amadoro ◽

Antonella Bobba ◽

Valentina Latina

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Mechanisms ◽

Food Product ◽

Neuroprotective Effects ◽

The Road ◽

Beneficial Effects ◽

Β Amyloid ◽

The Brain

A new epoch is emerging with intense research on nutraceuticals, i.e., “food or food product that provides medical or health benefits including the prevention and treatment of diseases”, such as Alzheimer’s disease. Nutraceuticals act at different biochemical and metabolic levels and much evidence shows their neuroprotective effects; in particular, they are able to provide protection against mitochondrial damage, oxidative stress, toxicity of β-amyloid and Tau and cell death. They have been shown to influence the composition of the intestinal microbiota significantly contributing to the discovery that differential microorganisms composition is associated with the formation and aggregation of cerebral toxic proteins. Further, the routes of interaction between epigenetic mechanisms and the microbiota–gut–brain axis have been elucidated, thus establishing a modulatory role of diet-induced epigenetic changes of gut microbiota in shaping the brain. This review examines recent scientific literature addressing the beneficial effects of some natural products for which mechanistic evidence to prevent or slowdown AD are available. Even if the road is still long, the results are already exceptional.

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Mitophagy in Alzheimer’s Disease and Other Age-Related Neurodegenerative Diseases

Cells ◽

10.3390/cells9010150 ◽

2020 ◽

Vol 9 (1) ◽

pp. 150 ◽

Cited By ~ 20

Author(s):

Qian Cai ◽

Yu Young Jeong

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Diseases ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Cellular Energy ◽

Age Related ◽

Mitochondrial Turnover ◽

Neuronal Functions ◽

Lateral Sclerosis

Mitochondrial dysfunction is a central aspect of aging and neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. Mitochondria are the main cellular energy powerhouses, supplying most of ATP by oxidative phosphorylation, which is required to fuel essential neuronal functions. Efficient removal of aged and dysfunctional mitochondria through mitophagy, a cargo-selective autophagy, is crucial for mitochondrial maintenance and neuronal health. Mechanistic studies into mitophagy have highlighted an integrated and elaborate cellular network that can regulate mitochondrial turnover. In this review, we provide an updated overview of the recent discoveries and advancements on the mitophagy pathways and discuss the molecular mechanisms underlying mitophagy defects in Alzheimer’s disease and other age-related neurodegenerative diseases, as well as the therapeutic potential of mitophagy-enhancing strategies to combat these disorders.

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

International Journal of Developmental Neuroscience ◽

10.1016/j.ijdevneu.2015.04.158 ◽

2015 ◽

Vol 47 (Part_A) ◽

pp. 56-56

Author(s):

Pardeep Kumar ◽

R.K. Kale ◽

N.Z. Baquer

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Therapeutic Potential ◽

Potential Drug ◽

Beneficial Effects

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Resveratrol and Neuroprotection: Impact and Its Therapeutic Potential in Alzheimer's Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2020.619024 ◽

2020 ◽

Vol 11 ◽

Author(s):

Md. Habibur Rahman ◽

Rokeya Akter ◽

Tanima Bhattacharya ◽

Mohamed M. Abdel-Daim ◽

Saad Alkahtani ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Neuroprotective Effect ◽

Tau Proteins ◽

Amyloid Peptides ◽

Work Done

Alzheimer’s disease (AD) is a progressive cortex and hippocampal neurodegenerative disease which ultimately causes cognitively impaired decline in patients. The AD pathogen is a very complex process, including aggregation of Aβ (β-amyloid peptides), phosphorylation of tau-proteins, and chronic inflammation. Exactly, resveratrol, a polyphenol present in red wine, and many plants are indicated to show the neuroprotective effect on mechanisms mostly above. Resveratrol plays an important role in promotion of non-amyloidogenic cleavage of the amyloid precursor protein. It also enhances the clearance of amyloid beta-peptides and reduces the damage of neurons. Most experimental research on AD and resveratrol has been performed in many species, both in vitro and in vivo, during the last few years. Nevertheless, resveratrol’s effects are restricted by its bioavailability in the reservoir. Therefore, scientists have tried to improve its efficiency by using different methods. This review focuses on recent work done on the cell and animal cultures and also focuses on the neuroprotective molecular mechanisms of resveratrol. It also discusses about the therapeutic potential onto the treatment of AD.

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Comparative study of the effects of phosphatidylcholine rich in DHA and EPA on Alzheimer's disease and the possible mechanisms in CHO-APP/PS1 cells and SAMP8 mice

Food & Function ◽

10.1039/c7fo01342f ◽

2018 ◽

Vol 9 (1) ◽

pp. 643-654 ◽

Cited By ~ 29

Author(s):

Hongxia Che ◽

Miaomiao Zhou ◽

Tiantian Zhang ◽

Lingyu Zhang ◽

Lin Ding ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Comparative Study ◽

Molecular Mechanisms ◽

Beneficial Effects ◽

Samp8 Mice

The beneficial effects of DHA-PC and EPA-PC on AD and the possible underlying molecular mechanisms.

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Triggering Innate Immune Receptors as New Therapies in Alzheimer’s Disease and Multiple Sclerosis

Cells ◽

10.3390/cells10082164 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2164

Author(s):

Pierre-Alexandre Piec ◽

Vincent Pons ◽

Serge Rivest

Keyword(s):

Multiple Sclerosis ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Innate Immunity ◽

Immune Cells ◽

Therapeutic Potential ◽

Innate Immune ◽

Innate Immune Cells ◽

Disease Course ◽

Beneficial Effects

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.

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Resveratrol as a Therapeutic Agent for Alzheimer’s Disease

BioMed Research International ◽

10.1155/2014/350516 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 50

Author(s):

Teng Ma ◽

Meng-Shan Tan ◽

Jin-Tai Yu ◽

Lan Tan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Mechanisms ◽

Therapeutic Agent ◽

Red Wine ◽

Therapeutic Potential ◽

Neuroprotective Effect ◽

Neuroprotective Effects

Alzheimer’s disease (AD) is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβaccumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD.

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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.

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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.

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