scholarly journals Liraglutide Has Anti-Inflammatory and Anti-Amyloid Properties in Streptozotocin-Induced and 5xFAD Mouse Models of Alzheimer’s Disease

2021 ◽  
Vol 22 (2) ◽  
pp. 860
Author(s):  
Leela Paladugu ◽  
Abeer Gharaibeh ◽  
Nivya Kolli ◽  
Cameron Learman ◽  
Tia C. Hall ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Insulin Signaling ◽  
Epidemiological Studies ◽  
Disease Stage ◽  
Brain State ◽  
Cognitive Changes ◽  
Neuroprotective Effects ◽  
Anti Inflammatory

Recent clinical and epidemiological studies support the contention that diabetes mellitus (DM) is a strong risk factor for the development of Alzheimer’s disease (AD). The use of insulin cell toxin, streptozotocin (STZ), when injected into the lateral ventricles, develops an insulin resistant brain state (IRBS) and represents a non-transgenic, or sporadic AD model (SAD), with several AD-like neuropathological features. The present study explored the effects of an anti-diabetic drug, liraglutide (LIR), in reversing major pathological hallmarks in the prodromal disease stage of both the 5xFAD transgenic and SAD mouse models of AD. Three-month-old 5xFAD and age-matched wild type mice were given a single intracerebroventricular (i.c.v) injection of STZ or vehicle (saline) and were subsequently treated with LIR, intraperitoneally (IP), once a day for 30 days. The extent of neurodegeneration, Aβ plaque load, and key proteins associated with the insulin signaling pathways were measured using Western blot and neuroinflammation (via immunohistological assays) in the cortical and hippocampal regions of the brain were assessed following a series of behavioral tests used to measure cognitive function after LIR or vehicle treatments. Our results indicated that STZ significantly increased neuroinflammation, Aβ plaque deposition and disrupted insulin signaling pathway, while 25 nmol/kg LIR, when injected IP, significantly decreased neuroinflammatory responses in both SAD and 5xFAD mice before significant cognitive changes were observed, suggesting LIR can reduce early neuropathology markers prior to the emergence of overt memory deficits. Our results indicate that LIR has neuroprotective effects and has the potential to serve as an anti-inflammatory and anti-amyloid prophylactic therapy in the prodromal stages of AD.

Astrocyte Reactivity in Alzheimer’s Disease: Therapeutic Opportunities to Promote Repair

2021 ◽  
Vol 18 ◽  
Author(s):  
Nazanin Mirzaei ◽  
Nicola Davis ◽  
Tsz Wing Chau ◽  
Magdalena Sastre
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mouse Models ◽  
Neurodegenerative Disorders ◽  
Amyloid Β ◽  
Neuroprotective Effects ◽  
Synaptic Density ◽  
Inflammatory Profile

: Astrocytes are fast climbing the ladder of importance in neurodegenerative disorders, particularly in Alzheimer’s disease (AD), with the prominent presence of reactive astrocytes sur- rounding amyloid β- plaques, together with activated microglia. Reactive astrogliosis, implying morphological and molecular transformations in astrocytes, seems to precede neurodegeneration, suggesting a role in the development of the disease. Single-cell transcriptomics has recently demon- strated that astrocytes from AD brains are different from “normal” healthy astrocytes, showing dys- regulations in areas such as neurotransmitter recycling, including glutamate and GABA, and im- paired homeostatic functions. However, recent data suggest that the ablation of astrocytes in mouse models of amyloidosis results in an increase in amyloid pathology as well as in the inflammatory profile and reduced synaptic density, indicating that astrocytes mediate neuroprotective effects. The idea that interventions targeting astrocytes may have great potential for AD has therefore emerged, supported by a range of drugs and stem cell transplantation studies that have successfully shown a therapeutic effect in mouse models of AD. In this article, we review the latest reports on the role and profile of astrocytes in AD brains and how manipulation of astrocytes in animal mod- els has paved the way for the use of treatments enhancing astrocytic function as future therapeutic avenues for AD.

scholarly journals Neuroprotective Mechanisms of Resveratrol in Alzheimer’s Disease: Role of SIRT1

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Bruno Alexandre Quadros Gomes ◽  
João Paulo Bastos Silva ◽  
Camila Fernanda Rodrigues Romeiro ◽  
Sávio Monteiro dos Santos ◽  
Caroline Azulay Rodrigues ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Vital Role ◽  
Hippocampal Damage ◽  
Neuroprotective Effects ◽  
Amyloid A ◽  
Silent Information Regulator 1 ◽  
Anti Inflammatory

Alzheimer’s disease (AD) is a progressive and neurodegenerative disorder of the cortex and hippocampus, which eventually leads to cognitive impairment. Although the etiology of AD remains unclear, the presence ofβ-amyloid (Aβ) peptides in these learning and memory regions is a hallmark of AD. Therefore, the inhibition of Aβpeptide aggregation has been considered the primary therapeutic strategy for AD treatment. Many studies have shown that resveratrol has antioxidant, anti-inflammatory, and neuroprotective properties and can decrease the toxicity and aggregation of Aβpeptides in the hippocampus of AD patients, promote neurogenesis, and prevent hippocampal damage. In addition, the antioxidant activity of resveratrol plays an important role in neuronal differentiation through the activation of silent information regulator-1 (SIRT1). SIRT1 plays a vital role in the growth and differentiation of neurons and prevents the apoptotic death of these neurons by deacetylating and repressing p53 activity; however, the exact mechanisms remain unclear. Resveratrol also has anti-inflammatory effects as it suppresses M1 microglia activation, which is involved in the initiation of neurodegeneration, and promotes Th2 responses by increasing anti-inflammatory cytokines and SIRT1 expression. This review will focus on the antioxidant and anti-inflammatory neuroprotective effects of resveratrol, specifically on its role in SIRT1 and the association with AD pathophysiology.

scholarly journals Anti-Inflammatory Activity of A Polyphenolic Extract from Arabidopsis thaliana in In Vitro and In Vivo Models of Alzheimer’s Disease

2019 ◽  
Vol 20 (3) ◽  
pp. 708 ◽  
Author(s):  
Roberto Mattioli ◽  
Antonio Francioso ◽  
Maria d’Erme ◽  
Maurizio Trovato ◽  
Patrizia Mancini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Arabidopsis Thaliana ◽  
Heme Oxygenase 1 ◽  
Neuroprotective Effects ◽  
In Vivo Models ◽  
Polyphenolic Extract ◽  
Anti Inflammatory ◽  
The Impact

Alzheimer’s disease (AD) is the most common neurodegenerative disorder and the primary form of dementia in the elderly. One of the main features of AD is the increase in amyloid-beta (Aβ) peptide production and aggregation, leading to oxidative stress, neuroinflammation and neurodegeneration. Polyphenols are well known for their antioxidant, anti-inflammatory and neuroprotective effects and have been proposed as possible therapeutic agents against AD. Here, we investigated the effects of a polyphenolic extract of Arabidopsis thaliana (a plant belonging to the Brassicaceae family) on inflammatory response induced by Aβ. BV2 murine microglia cells treated with both Aβ25–35 peptide and extract showed a lower pro-inflammatory (IL-6, IL-1β, TNF-α) and a higher anti-inflammatory (IL-4, IL-10, IL-13) cytokine production compared to cells treated with Aβ only. The activation of the Nrf2-antioxidant response element signaling pathway in treated cells resulted in the upregulation of heme oxygenase-1 mRNA and in an increase of NAD(P)H:quinone oxidoreductase 1 activity. To establish whether the extract is also effective against Aβ-induced neurotoxicity in vivo, we evaluated its effect on the impaired climbing ability of AD Drosophila flies expressing human Aβ1–42. Arabidopsis extract significantly restored the locomotor activity of these flies, thus confirming its neuroprotective effects also in vivo. These results point to a protective effect of the Arabidopsis extract in AD, and prompt its use as a model in studying the impact of complex mixtures derived from plant-based food on neurodegenerative diseases.

scholarly journals A Review: Inflammatory Process in Alzheimer's Disease, Role of Cytokines

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Jose Miguel Rubio-Perez ◽  
Juana Maria Morillas-Ruiz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Process ◽  
Transforming Growth Factor ◽  
Neurodegenerative Disorder ◽  
Epidemiological Studies ◽  
Brain Disorder ◽  
Amyloid A ◽  
Cytokines And Chemokines ◽  
Anti Inflammatory

Alzheimer's disease (AD) is the most common neurodegenerative disorder to date. Neuropathological hallmarks areβ-amyloid (Aβ) plaques and neurofibrillary tangles, but the inflammatory process has a fundamental role in the pathogenesis of AD. Inflammatory components related to AD neuroinflammation include brain cells such as microglia and astrocytes, the complement system, as well as cytokines and chemokines. Cytokines play a key role in inflammatory and anti-inflammatory processes in AD. An important factor in the onset of inflammatory process is the overexpression of interleukin (IL)-1, which produces many reactions in a vicious circle that cause dysfunction and neuronal death. Other important cytokines in neuroinflammation are IL-6 and tumor necrosis factor (TNF)-α. By contrast, other cytokines such as IL-1 receptor antagonist (IL-1ra), IL-4, IL-10, and transforming growth factor (TGF)-βcan suppress both proinflammatory cytokine production and their action, subsequently protecting the brain. It has been observed in epidemiological studies that treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the risk for developing AD. Unfortunately, clinical trials of NSAIDs in AD patients have not been very fruitful. Proinflammatory responses may be countered through polyphenols. Supplementation of these natural compounds may provide a new therapeutic line of approach to this brain disorder.

A positive allosteric modulator of mGluR5 promotes neuroprotective effects in mouse models of Alzheimer's disease

2019 ◽  
Vol 160 ◽  
pp. 107785 ◽  
Author(s):  
Paula Maria Quaglio Bellozi ◽  
Giovanni Freitas Gomes ◽  
Maria Carolina Machado da Silva ◽  
Isabel Vieira de Assis Lima ◽  
Carla Ribeiro Álvares Batista ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Neuroprotective Effects

scholarly journals Cognitive Changes associated with Alzheimer’s disease in Down syndrome

2018 ◽  
Author(s):  
Nicholas C. Firth ◽  
Carla M. Startin ◽  
Rosalyn Hithersay ◽  
Sarah Hamburg ◽  
Peter A. Wijeratne ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Cognitive Decline ◽  
Sustained Attention ◽  
Motor Coordination ◽  
Disease Stage ◽  
Cognitive Test ◽  
Early Assessment ◽  
Cognitive Changes

AbstractObjectiveIndividuals with Down syndrome (DS) have an extremely high genetic risk for Alzheimer’s disease (AD) however the course of cognitive decline associated with progression to dementia is ill-defined. Data-driven methods can estimate long-term trends from cross-sectional data while adjusting for variability in baseline ability, which complicates dementia assessment in those with DS.MethodsWe applied an event-based model to cognitive test data and informant-rated questionnaire data from 283 adults with DS (the largest study of cognitive functioning in DS to date) to estimate the sequence of cognitive decline and individuals’ disease stage.ResultsDecline in tests of memory, sustained attention / motor coordination, and verbal fluency occurred early, demonstrating that AD in DS follows a similar pattern of change to other forms of AD. Later decline was found for informant measures. Using the resulting staging model, we showed that adults with a clinical diagnosis of dementia and those with APOE 3:4 or 4:4 genotype were significantly more likely to be staged later, suggesting the model is valid.InterpretationOur results identify tests of memory and sustained attention may be particularly useful measures to track decline in the preclinical/prodromal stages of AD in DS whereas informant-measures may be useful in later stages (i.e. during conversion to dementia, or post-diagnosis). These results have implications for the selection of outcome measures of treatment trials to delay or prevent cognitive decline due to AD in DS. As clinical diagnoses are generally made late into AD progression, early assessment is essential.

scholarly journals The Neuroprotective Effects of Moderate and Regular Caffeine Consumption in Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Xiangyu Zhou ◽  
Lin Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Epidemiological Studies ◽  
Experimental Models ◽  
Caffeine Intake ◽  
Steady Increase ◽  
Caffeine Consumption ◽  
Neuroprotective Effects ◽  
Relationship Of

The increasing numbers of elderly Alzheimer’s disease (AD) patients because of a steady increase in the average lifespan and aging society attract great scientific concerns, while there were fewer effective treatments on AD progression due to unclear exact causes and pathogenesis of AD. Moderate (200-500 mg/d) and regular caffeine consumption from coffee and tea are considered to alleviate the risk of AD and have therapeutic potential. This paper reviewed epidemiological studies about the relationship of caffeine intake from coffee or/and tea with the risk of AD and summarized the caffeine-related AD therapies based on experimental models. And further well-designed and well-conducted studies are suggested to investigate the optimal dosages, frequencies, and durations of caffeine consumption to slow down AD progression and treat AD.

scholarly journals REVIEW ON EVALUATING THE ROLE OF NSAIDS FOR THE TREATMENT OF ALZHEIMER'S DISEASE

2021 ◽  
pp. 91-94
Author(s):  
KRISHNENDU P. R. ◽  
ARJUN B. ◽  
VIBINA K. ◽  
NIVEA CLEO T. S. ◽  
DRISYA N. K. ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorders ◽  
Symptomatic Relief ◽  
Drug Repurposing ◽  
Epidemiological Studies ◽  
Neuroprotective Activity ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
The Cost

Recently, several studies have been reported that nonsteroidal anti-inflammatory drugs can fight against neurodegenerative disorders by various mechanisms. Currently, available therapies of neurodegenerative disorders (NDs) provide only symptomatic relief. This is the point at which we need an alternative that acts on the root cause of disease. Parkinson’s disease and Alzheimer’s disease are the two NDs concentrated here. Since the drug profile is already known, drug repurposing is a promising technique in research, thereby reducing the cost and period effectively. Epidemiological studies on various nonsteroidal anti-inflammatory drugs (NSAIDs) showed good results, but when it came to clinical studies the results are found to be poor. Hence, it can be concluded that NSAIDs provide its neuroprotective activity on its long-term use only, as the brain accessibility of this kind of drug is poor due to its lower lipophilicity.

Sign in / Sign up

Export Citation Format

Share Document