Exploring the Anti-Neuroinflammatory Potential of Steroid and Terpenoid-Derived Phytochemicals to Combat Alzheimer's Disease

2021 ◽  
Vol 26 ◽  
Author(s):  
Md. Tanvir Kabir ◽  
Md. Sahab Uddin ◽  
Sonia Zaman ◽  
Md. Sohanur Rahman ◽  
Tapan Behl ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Symptomatic Treatment ◽  
Drug Candidates ◽  
Age Related ◽  
Inflammatory Processes ◽  
Pharmacologically Active ◽  
And Behavior ◽  
Therapeutic Activities

: Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder that significantly affects cognitive functions in a way that causes loss of memory, thinking, and behavior. Multiple studies revealed that neuroinflammation associated with AD is linked with the amyloid-beta deposition in the brain. Elevated levels of expression of cytokines, microglial activation, nuclear factor kappa B, and reactive oxygen species play roles in ADrelated inflammatory processes. Indeed, effective therapeutic approaches are urgently required to develop therapeutic agents to prevent and treat AD. So far, many anti-AD drug candidates have failed in the clinical stages and currently available drugs only provide symptomatic treatment. In recent times, pharmacologically active phytochemicals have been found to possess promising anti-neuroinflammatory effects; therefore these natural products can be useful in the AD treatment. In this review, we have comprehensively discussed the role of neuroinflammation and the molecular processes altered by multiple steroid and terpenoid-derived phytochemicals in various AD-related neuroinflammatory pathways. Indeed, steroid and terpenoid-derived phytochemicals show important therapeutic activities, which can be useful in ameliorating and treating AD-related neurodegeneration.

scholarly journals The Impact of Systemic Inflammation on Alzheimer’s Disease Pathology

2022 ◽  
Vol 12 ◽  
Author(s):  
Junhua Xie ◽  
Lien Van Hoecke ◽  
Roosmarijn E. Vandenbroucke
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rational Design ◽  
Neurodegenerative Disorder ◽  
Peripheral Inflammation ◽  
Comprehensive Overview ◽  
Age Related ◽  
Symptomatic Medication ◽  
Inflammatory Processes ◽  
The Impact

Alzheimer’s disease (AD) is a devastating age-related neurodegenerative disorder with an alarming increasing prevalence. Except for the recently FDA-approved Aducanumab of which the therapeutic effect is not yet conclusively proven, only symptomatic medication that is effective for some AD patients is available. In order to be able to design more rational and effective treatments, our understanding of the mechanisms behind the pathogenesis and progression of AD urgently needs to be improved. Over the last years, it became increasingly clear that peripheral inflammation is one of the detrimental factors that can contribute to the disease. Here, we discuss the current understanding of how systemic and intestinal (referred to as the gut-brain axis) inflammatory processes may affect brain pathology, with a specific focus on AD. Moreover, we give a comprehensive overview of the different preclinical as well as clinical studies that link peripheral Inflammation to AD initiation and progression. Altogether, this review broadens our understanding of the mechanisms behind AD pathology and may help in the rational design of further research aiming to identify novel therapeutic targets.

Emerging Promise of Immunotherapy for Alzheimer’s Disease: A New Hope for the Development of Alzheimer’s Vaccine

2020 ◽  
Vol 20 (13) ◽  
pp. 1214-1234 ◽  
Author(s):  
Md. Tanvir Kabir ◽  
Md. Sahab Uddin ◽  
Bijo Mathew ◽  
Pankoj Kumar Das ◽  
Asma Perveen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Response ◽  
Neutralizing Antibodies ◽  
Neurodegenerative Disorder ◽  
Symptomatic Relief ◽  
Aβ Oligomers ◽  
Th2 Immune Response ◽  
Age Related ◽  
Anti Inflammatory

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the characteristics of this devastating disorder include the progressive and disabling deficits in the cognitive functions including reasoning, attention, judgment, comprehension, memory, and language. Objective: In this article, we have focused on the recent progress that has been achieved in the development of an effective AD vaccine. Summary: Currently, available treatment options of AD are limited to deliver short-term symptomatic relief only. A number of strategies targeting amyloid-beta (Aβ) have been developed in order to treat or prevent AD. In order to exert an effective immune response, an AD vaccine should contain adjuvants that can induce an effective anti-inflammatory T helper 2 (Th2) immune response. AD vaccines should also possess the immunogens which have the capacity to stimulate a protective immune response against various cytotoxic Aβ conformers. The induction of an effective vaccine’s immune response would necessitate the parallel delivery of immunogen to dendritic cells (DCs) and their priming to stimulate a Th2-polarized response. The aforesaid immune response is likely to mediate the generation of neutralizing antibodies against the neurotoxic Aβ oligomers (AβOs) and also anti-inflammatory cytokines, thus preventing the AD-related inflammation. Conclusion: Since there is an age-related decline in the immune functions, therefore vaccines are more likely to prevent AD instead of providing treatment. AD vaccines might be an effective and convenient approach to avoid the treatment-related huge expense.

scholarly journals Relationship between Wine Consumption, Diet and Microbiome Modulation in Alzheimer’s Disease

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3082
Author(s):  
M. Victoria Moreno-Arribas ◽  
Begoña Bartolomé ◽  
José L. Peñalvo ◽  
Patricia Pérez-Matute ◽  
Maria José Motilva
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Intestinal Microbiome ◽  
Dietary Polyphenols ◽  
Age Related ◽  
Wine Polyphenols ◽  
The Impact

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder leading to the most common form of dementia in elderly people. Modifiable dietary and lifestyle factors could either accelerate or ameliorate the aging process and the risk of developing AD and other age-related morbidities. Emerging evidence also reports a potential link between oral and gut microbiota alterations and AD. Dietary polyphenols, in particular wine polyphenols, are a major diver of oral and gut microbiota composition and function. Consequently, wine polyphenols health effects, mediated as a function of the individual’s oral and gut microbiome are considered one of the recent greatest challenges in the field of neurodegenerative diseases as a promising strategy to prevent or slow down AD progression. This review highlights current knowledge on the link of oral and intestinal microbiome and the interaction between wine polyphenols and microbiota in the context of AD. Furthermore, the extent to which mechanisms bacteria and polyphenols and its microbial metabolites exert their action on communication pathways between the brain and the microbiota, as well as the impact of the molecular mediators to these interactions on AD patients, are described.

scholarly journals Repositioning of Immunomodulators: A Ray of Hope for Alzheimer’s Disease?

2020 ◽  
Vol 14 ◽  
Author(s):  
Antonio Munafò ◽  
Chiara Burgaletto ◽  
Giulia Di Benedetto ◽  
Marco Di Mauro ◽  
Rosaria Di Mauro ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Neurodegenerative Disorder ◽  
Drug Repositioning ◽  
Amyloid Β ◽  
Deep Understanding ◽  
Current Status ◽  
Age Related ◽  
Tnf Α

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder characterized by cognitive decline and by the presence of amyloid β plaques and neurofibrillary tangles in the brain. Despite recent advances in understanding its pathophysiological mechanisms, to date, there are no disease-modifying therapeutic options, to slow or halt the evolution of neurodegenerative processes in AD. Current pharmacological treatments only transiently mitigate the severity of symptoms, with modest or null overall improvement. Emerging evidence supports the concept that AD is affected by the impaired ability of the immune system to restrain the brain’s pathology. Deep understanding of the relationship between the nervous and the immune system may provide a novel arena to develop effective and safe drugs for AD treatment. Considering the crucial role of inflammatory/immune pathways in AD, here we discuss the current status of the immuno-oncological, immunomodulatory and anti-TNF-α drugs which are being used in preclinical studies or in ongoing clinical trials by means of the drug-repositioning approach.

Clinical course of Alzheimer’s disease

2011 ◽  
Author(s):  
Alberto Lleo ◽  
Rafael Blesa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Daily Living ◽  
Clinical Course ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Remote Memory ◽  
Initial Symptom ◽  
Delayed Recall ◽  
Age Related

• Alzheimer’s disease is an age-related neurodegenerative disorder, with onset usually in late life, characterized by cognitive impairment, a variety of behavioural symptoms, and restrictions in the activities of daily living• The initial symptom is episodic memory loss, in particular in delayed recall of visual and/or verbal material. Immediate and remote memory is usually preserved in early stages...

scholarly journals Protein Homeostasis Networks and the Use of Yeast to Guide Interventions in Alzheimer’s Disease

2020 ◽  
Vol 21 (21) ◽  
pp. 8014
Author(s):  
Sudip Dhakal ◽  
Ian Macreadie
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stress Responses ◽  
Cell Biology ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Yeast Cells ◽  
Yeast Genome ◽  
Protein Homeostasis ◽  
Age Related

Alzheimer’s Disease (AD) is a progressive multifactorial age-related neurodegenerative disorder that causes the majority of deaths due to dementia in the elderly. Although various risk factors have been found to be associated with AD progression, the cause of the disease is still unresolved. The loss of proteostasis is one of the major causes of AD: it is evident by aggregation of misfolded proteins, lipid homeostasis disruption, accumulation of autophagic vesicles, and oxidative damage during the disease progression. Different models have been developed to study AD, one of which is a yeast model. Yeasts are simple unicellular eukaryotic cells that have provided great insights into human cell biology. Various yeast models, including unmodified and genetically modified yeasts, have been established for studying AD and have provided significant amount of information on AD pathology and potential interventions. The conservation of various human biological processes, including signal transduction, energy metabolism, protein homeostasis, stress responses, oxidative phosphorylation, vesicle trafficking, apoptosis, endocytosis, and ageing, renders yeast a fascinating, powerful model for AD. In addition, the easy manipulation of the yeast genome and availability of methods to evaluate yeast cells rapidly in high throughput technological platforms strengthen the rationale of using yeast as a model. This review focuses on the description of the proteostasis network in yeast and its comparison with the human proteostasis network. It further elaborates on the AD-associated proteostasis failure and applications of the yeast proteostasis network to understand AD pathology and its potential to guide interventions against AD.

scholarly journals Pleiotropic Protective Effects of Phytochemicals in Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sergio Davinelli ◽  
Nadia Sapere ◽  
Davide Zella ◽  
Renata Bracale ◽  
Mariano Intrieri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Protective Effects ◽  
Drug Candidates ◽  
Molecular Events ◽  
Therapeutic Value ◽  
Phytochemical Compounds ◽  
Multiple Levels ◽  
The Brain

Alzheimer’s disease (AD) is a severe chronic neurodegenerative disorder of the brain characterised by progressive impairment in memory and cognition. In the past years an intense research has aimed at dissecting the molecular events of AD. However, there is not an exhaustive knowledge about AD pathogenesis and a limited number of therapeutic options are available to treat this neurodegenerative disease. Consequently, considering the heterogeneity of AD, therapeutic agents acting on multiple levels of the pathology are needed. Recent findings suggest that phytochemicals compounds with neuroprotective features may be an important resources in the discovery of drug candidates against AD. In this paper we will describe some polyphenols and we will discuss their potential role as neuroprotective agents. Specifically, curcumin, catechins, and resveratrol beyond their antioxidant activity are also involved in antiamyloidogenic and anti-inflammatory mechanisms. We will focus on specific molecular targets of these selected phytochemical compounds highlighting the correlations between their neuroprotective functions and their potential therapeutic value in AD.

scholarly journals The Triggering Receptor Expressed on Myeloid Cells 2: “TREM-ming” the Inflammatory Component Associated with Alzheimer's Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Troy T. Rohn
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Senile Plaques ◽  
Myeloid Cells ◽  
Disease Process ◽  
Age Related

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by a progressive loss of memory and cognitive skills. Although much attention has been devoted concerning the contribution of the microscopic lesions, senile plaques, and neurofibrillary tangles to the disease process, inflammation has long been suspected to play a major role in the etiology of AD. Recently, a novel variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight back onto inflammation as a major contributing factor in AD. Variants in TREM2 triple one's risk of developing late-onset AD. TREM2 is expressed on microglial cells, the resident macrophages in the CNS, and functions to stimulate phagocytosis on one hand and to suppress cytokine production and inflammation on the other hand. The purpose of this paper is to discuss these recent developments including the potential role that TREM2 normally plays and how loss of function may contribute to AD pathogenesis by enhancing oxidative stress and inflammation within the CNS. In this context, an overview of the pathways linking beta-amyloid, neurofibrillary tangles (NFTs), oxidative stress, and inflammation will be discussed.

scholarly journals A Chinese Herbal Formula, Gengnianchun, Amelioratesβ-Amyloid Peptide Toxicity in aCaenorhabditis elegansModel of Alzheimer’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Fanhui Meng ◽  
Jun Li ◽  
Yanqiu Rao ◽  
Wenjun Wang ◽  
Yan Fu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Amyloid Peptide ◽  
Mrna Levels ◽  
Pheochromocytoma Cells ◽  
C Elegans ◽  
Chinese Herbal ◽  
Chinese Medicine Formula ◽  
Age Related

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder, and the few drugs that are currently available only treat the symptoms. Traditional medicine or phytotherapy has been shown to protect against AD. In our previous studies, Gengnianchun (GNC), a traditional Chinese medicine formula with a prolongevity effect, protected against Aβ-induced cytotoxicity in pheochromocytoma cells (PC-12 cells) and hippocampal cells. Here, we investigated the effects and possible mechanisms by which GNC protected against Aβtoxicity using transgenicCaenorhabditis elegansCL4176. Our results showed that GNC effectively delayed the Aβtoxicity-triggered body paralysis of CL4176 worms. GNC decreased Aβby reducing AβmRNA levels. Moreover, GNC significantly reduced reactive oxygen species in the AD model worms compared with the controls. In addition, GNC upregulated the daf-16, sod-3, hsp-16.2 genes, and enhanced DAF-16 translocation from the cytoplasm to the nuclei under oxidative stress conditions. GNC treatment ofC. elegansstrains lacking DAF-16 did not affect the paralysis phenotype. Taken together, these findings suggest that GNC could protect against Aβ-induced toxicity via the DAF-16 pathway inC. elegans. Further studies are required to analyze its effectiveness in more complex animals.

scholarly journals Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyondβ-Amyloid: Insights from Clinical Trials

2014 ◽  
Vol 2014 ◽  
pp. 1-22 ◽  
Author(s):  
Qiutian Jia ◽  
Yulin Deng ◽  
Hong Qing
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Drug Targets ◽  
Neurodegenerative Disorder ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Drug Candidates ◽  
Effective Drugs ◽  
Novel Drug

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with two hallmarks:β-amyloid plagues and neurofibrillary tangles. It is one of the most alarming illnesses to elderly people. No effective drugs and therapies have been developed, while mechanism-based explorations of therapeutic approaches have been intensively investigated. Outcomes of clinical trials suggested several pitfalls in the choice of biomarkers, development of drug candidates, and interaction of drug-targeted molecules; however, they also aroused concerns on the potential deficiency in our understanding of pathogenesis of AD, and ultimately stimulated the advent of novel drug targets tests. The anticipated increase of AD patients in next few decades makes development of better therapy an urgent issue. Here we attempt to summarize and compare putative therapeutic strategies that have completed clinical trials or are currently being tested from various perspectives to provide insights for treatments of Alzheimer’s disease.

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