scholarly journals Resveratrol, Metabolic Dysregulation, and Alzheimer’s Disease: Considerations for Neurogenerative Disease

2021 ◽  
Vol 22 (9) ◽  
pp. 4628
Author(s):  
Alex J. T. Yang ◽  
Ahmed Bagit ◽  
Rebecca E. K. MacPherson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Metabolic Disorders ◽  
Synaptic Function ◽  
Metabolic Dysregulation ◽  
Beta Peptide ◽  
The Brain ◽  
Metabolic Impairments

Alzheimer’s disease (AD) has traditionally been discussed as a disease where serious cognitive decline is a result of Aβ-plaque accumulation, tau tangle formation, and neurodegeneration. Recently, it has been shown that metabolic dysregulation observed with insulin resistance and type-2 diabetes actively contributes to the progression of AD. One of the pathologies linking metabolic disease to AD is the release of inflammatory cytokines that contribute to the development of brain neuroinflammation and mitochondrial dysfunction, ultimately resulting in amyloid-beta peptide production and accumulation. Improving these metabolic impairments has been shown to be effective at reducing AD progression and improving cognitive function. The polyphenol resveratrol (RSV) improves peripheral metabolic disorders and may provide similar benefits centrally in the brain. RSV reduces inflammatory cytokine release, improves mitochondrial energetic function, and improves Aβ-peptide clearance by activating SIRT1 and AMPK. RSV has also been linked to improved cognitive function; however, the mechanisms of action are less defined. However, there is evidence to suggest that chronic RSV-driven AMPK activation may be detrimental to synaptic function and growth, which would directly impact cognition. This review will discuss the benefits and adverse effects of RSV on the brain, highlighting the major signaling pathways and some of the gaps surrounding the use of RSV as a treatment for AD.

scholarly journals Ameliorating amyloid aggregation through osmolytes as a probable therapeutic molecule against Alzheimer's disease and type 2 diabetes

RSC Advances ◽  
2020 ◽  
Vol 10 (21) ◽  
pp. 12166-12182
Author(s):  
Anchala Kumari ◽  
Pallavi Somvanshi ◽  
Abhinav Grover
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Metabolic Disorders ◽  
Misfolded Proteins ◽  
Amyloid Aggregation ◽  
Large Numbers

Large numbers of neurological and metabolic disorders occurring in humans are induced by the aberrant growth of aggregated or misfolded proteins.

scholarly journals Mitochondrial Dysfunctions: A Thread Sewing Together Alzheimer’s Disease, Diabetes, and Obesity

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Giulia Rigotto ◽  
Emy Basso
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Environmental Factors ◽  
Metabolic Disorders ◽  
Mitochondrial Dysfunctions ◽  
Mitochondrial Alterations ◽  
Multiple Genes ◽  
Diabetes And Obesity

Metabolic disorders are severe and chronic impairments of the health of many people and represent a challenge for the society as a whole that has to deal with an ever-increasing number of affected individuals. Among common metabolic disorders are Alzheimer’s disease, obesity, and type 2 diabetes. These disorders do not have a univocal genetic cause but rather can result from the interaction of multiple genes, lifestyle, and environmental factors. Mitochondrial alterations have emerged as a feature common to all these disorders, underlining perhaps an impaired coordination between cellular needs and mitochondrial responses that could contribute to their development and/or progression.

scholarly journals Quinacrine directly dissociates amyloid plaques in the brain of 5XFAD transgenic mouse model of Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sohui Park ◽  
Hye Yun Kim ◽  
Hyun-A Oh ◽  
Jisu Shin ◽  
In Wook Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Weight ◽  
Transgenic Mice ◽  
Cortical Neurons ◽  
Amyloid Β ◽  
Synaptic Function ◽  
Western Blots ◽  
Aβ Fibrils ◽  
The Brain

AbstractAlzheimer’s disease (AD) is the most common type of dementia characterized by the abnormal accumulation of amyloid-β (Aβ) in the brain. Aβ misfolding is associated with neuroinflammation and synaptic dysfunction, leading to learning and memory deficits. Therefore, Aβ production and aggregation have been one of the most popular drug targets for AD. Failures of drug candidates regulating the aforementioned Aβ cascade stimulated development of immunotherapy agents for clearance of accumulated Aβ in the brain. Here, we report that quinacrine, a blood–brain barrier penetrating antimalarial chemical drug, dissociates Aβ plaques in the brain of AD transgenic mice. When co-incubated with pre-formed Aβ fibrils, quinacrine decreased thioflavin T-positive β-sheets in vitro, on top of its inhibitory function on the fibril formation. We confirmed that quinacrine induced dissociation of high-molecular-weight Aβ aggregates into low-molecular-weight species by dot blots in association with size cut-off filtrations. Quinacrine was then administered to adult 5XFAD transgenic mice via weekly intravenous injections for 6 weeks, and we found a significant reduction of Aβ plaques and astrocytosis in their cortex and hippocampus. In western blots of quinacrine-administered mouse brains, amelioration of AD-related biomarkers, glial fibrillary acidic protein, postsynaptic protein 95, phosphorylated cAMP response element-binding protein, phosphorylated c-Jun N-terminal kinase were observed. Lastly, quinacrine-stimulated dissociation of misfolded aggregates induced recovery of synaptic function associated with Aβ in excitatory post-synaptic current recordings of primary rat cortical neurons treated with Aβ aggregates and quinacrine. Collectively, quinacrine can directly dissociate Aβ fibrils and alleviate decreased synaptic functions.

Nanoparticles in the Treatment of Alzheimer’s Disease with Magnetic Resonance

2021 ◽  
Vol 13 (7) ◽  
pp. 1350-1357
Author(s):  
Yingjun Zhang ◽  
Wubing Mao ◽  
Min Feng ◽  
Ning Zhu ◽  
Wenzhong Yi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Magnetic Resonance ◽  
Model Group ◽  
Sd Rats ◽  
Group A ◽  
Group B ◽  
Group D ◽  
The Brain

ABSTRACTThis study was to explore the effect of nanoparticles on the cognitive function, learning and memory ability (LMA) of Alzheimer’s disease (AD) rats, and to analyze the changes on magnetic resonance (MR) image. Specifically, the TGN nanoparticles loading H102 (TGN-NP-H102) were prepared, and characterized first. The sprague-dawley (SD) rats were selected as the research subjects, and the AD model was constructed. They were divided into a Sham group (normal SD rats, group A), an AD model group (group B), an H102 group (treated with H102 drugs based on AD model, group C), and a TGN-NP-H102 group (treated with TGN-NP-H102 nanoparticles based on AD model, group D). The changes in T2 value in hippocampal CA1 area (T2-CA1) were analyzed, and the changes in cognitive function and LMA were tested with the Morris water maze experiment (Morris experiment). The results revealed that, the average PS (APS) of TGN-NP-H102 nanoparticles was 122.9±2.8 nm, and its average Zeta potential (AZP) was -28.8±0.2 mV. In group A, the TGN-NP-H102 nanoparticles still remained in the brain tissue homogenate by 74.3 ±4.8% after 10 hours, and the drug-release rate was 53.2 ± 3.2%. After 30 days of treatment, the T2-CA1 value of group D was lower (P <0.05), and the average escape latency (AEL) and swimming distance in the Morris experiment were shorter versus group B (P < 0.05). It indicated that, the brain-targeted TGN-NP-H102 nanoparticles prepared could act on the hippocampus of AD rats, and improve their LMA.

scholarly journals Synergistic effects of hypertension and aging on cognitive function and hippocampal expression of genes involved in β-amyloid generation and Alzheimer's disease

2013 ◽  
Vol 305 (8) ◽  
pp. H1120-H1130 ◽  
Author(s):  
Anna Csiszar ◽  
Zsuzsanna Tucsek ◽  
Peter Toth ◽  
Danuta Sosnowska ◽  
Tripti Gautam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Protein Binding ◽  
Synergistic Effects ◽  
Amyloid Β ◽  
Synaptic Function ◽  
Precursor Protein ◽  
Expression Of Genes ◽  
Β Amyloid

Strong epidemiological and experimental evidence indicate that hypertension in the elderly predisposes to the development of Alzheimer's disease (AD), but the underlying mechanisms remain elusive. The present study was designed to characterize the additive/synergistic effects of hypertension and aging on the expression of genes involved in β-amyloid generation and AD in the hippocampus, an area of brain contributing to higher cognitive function, which is significantly affected by AD both in humans and in mouse models of the disease. To achieve that goal, we induced hypertension in young (3 mo) and aged (24 mo) C57BL/6 mice by chronic (4 wk) infusion of angiotensin II and assessed changes in hippocampal mRNA expression of genes involved in amyloid precursor protein (APP)-dependent signaling, APP cleavage, Aβ processing and Aβ-degradation, synaptic function, dysregulation of microtubule-associated τ protein, and apolipoprotein-E signaling. Aged hypertensive mice exhibited spatial memory impairments in the Y-maze and impaired performance in the novel object recognition assay. Surprisingly, hypertension in aging did not increase the expression of APP, β- and γ-secretases, or genes involved in tauopathy. These genes are all involved in the early onset form of AD. Yet, hypertension in aging was associated with changes in hippocampal expression of APP binding proteins, e.g., [Mint3/amyloid β A4 precursor protein-binding family A member 3 (APBA3), Fe65/amyloid β A4 precursor protein-binding family B member 1 (APBB1)], amyloid β (A4) precursor-like protein 1 (APLP1), muscarinic M1 receptor, and serum amyloid P component, all of which may have a role in the pathogenesis of late-onset AD. The hippocampal gene expression signature observed in aged hypertensive mice in the present study provides important clues for subsequent studies to elucidate the mechanisms by which hypertension may contribute to the pathogenesis and clinical manifestation of AD.

scholarly journals Amyloid-Beta Peptide, Oxidative Stress and Inflammation in Alzheimer's Disease: Potential Neuroprotective Effects of Omega-3 Polyunsaturated Fatty Acids

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
S. C. Dyall
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Amyloid Peptide ◽  
Omega 3 ◽  
Neuroprotective Effects ◽  
Beta Peptide ◽  
The Brain

Alzheimer's disease is the most common form of dementia in the elderly and is a progressive neurodegenerative disorder characterised by a decline in cognitive function and also profound alterations in mood and behaviour. The pathology of the disease is characterised by the presence of extracellular amyloid peptide deposits and intracellular neurofibrillary tangles in the brain. Although many hypotheses have been put forward for the aetiology of the disease, increased inflammation and oxidative stress appear key to be features contributing to the pathology. The omega-3 polyunsaturated fats, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have well-characterised effects on inflammation and may have neuroprotective effects in a number of neurodegenerative conditions including Alzheimer's disease. The aims of this paper are to review the neuroprotective effects of EPA and DHA in Alzheimer's disease, with special emphasis on their role in modulating oxidative stress and inflammation and also examine their potential as therapeutic agents.

scholarly journals Cognitive Function Improvement in Mouse Model of Alzheimer’s Disease Following Transcranial Direct Current Stimulation

2020 ◽  
Vol 10 (8) ◽  
pp. 547
Author(s):  
Wang-In Kim ◽  
Jae-Young Han ◽  
Min-Keun Song ◽  
Hyeng-Kyu Park ◽  
Jihoon Jo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mouse Model ◽  
Direct Current ◽  
Transcranial Direct Current Stimulation ◽  
Wild Type ◽  
Direct Current Stimulation ◽  
Induction Group ◽  
The Brain

Anodal transcranial direct current stimulation (tDCS) is a painless noninvasive method that reportedly improves cognitive function in Alzheimer’s disease (AD) by stimulating the brain. However, its underlying mechanism remains unclear. Thus, the present study investigates the cognitive effects in a 5xFAD AD mouse model using electrophysiological and pathological methods. We used male 5xFAD C57BL/6J and male C57BL/6J wild-type mice; the dementia model was confirmed through DNA sequencing. The verified AD and wild-type mice were randomly assigned into four groups of five mice each: an induced AD group receiving tDCS treatment (Stim-AD), an induced AD group not receiving tDCS (noStim-AD), a non-induction group receiving tDCS (Stim-WT), and a non-induction group not receiving tDCS (noStim-WT). In the Stim group, mice received tDCS in the frontal bregma areas at an intensity of 200 µA for 20 min. After 2 weeks of treatment, we decapitated the mice, removed the hippocampus from the brain, confirmed its neuronal activation through excitatory postsynaptic potential (EPSP) recording, and performed molecular experiments on the remaining tissue using western blots. EPSP significantly increased in the Stim-AD group compared to that in the noStim-AD, which was comparable to that in the non-induced groups, Stim-WT and noStim-WT. There were no significant differences in cyclic amp-response element binding protein (CREB), phosphorylated CREB (pCREB), and Brain-derived neurotrophic factor (BDNF) levels in the Stim-AD group compared to those in the noStim-AD group. This study demonstrated that a tDCS in both frontal lobes of a transgenic 5xFAD mouse model affects long-term potentiation, indicating possible enhancement of cognitive function.

scholarly journals Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1983
Author(s):  
Erika Kropf ◽  
Margaret Fahnestock
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Basal Forebrain ◽  
Memory Loss ◽  
Reactive Oxygen ◽  
Neurotrophin Receptor ◽  
Nitrogen Species ◽  
Age Related ◽  
The Brain

Nerve growth factor (NGF) and its precursor form, proNGF, are critical for neuronal survival and cognitive function. In the brain, proNGF is the only detectable form of NGF. Dysregulation of proNGF in the brain is implicated in age-related memory loss and Alzheimer’s disease (AD). AD is characterized by early and progressive degeneration of the basal forebrain, an area critical for learning, memory, and attention. Learning and memory deficits in AD are associated with loss of proNGF survival signalling and impaired retrograde transport of proNGF to the basal forebrain. ProNGF transport and signalling may be impaired by the increased reactive oxygen and nitrogen species (ROS/RNS) observed in the aged and AD brain. The current literature suggests that ROS/RNS nitrate proNGF and reduce the expression of the proNGF receptor tropomyosin-related kinase A (TrkA), disrupting its downstream survival signalling. ROS/RNS-induced reductions in TrkA expression reduce cell viability, as proNGF loses its neurotrophic function in the absence of TrkA and instead generates apoptotic signalling via the pan-neurotrophin receptor p75NTR. ROS/RNS also interfere with kinesin and dynein motor functions, causing transport deficits. ROS/RNS-induced deficits in microtubule motor function and TrkA expression and signalling may contribute to the vulnerability of the basal forebrain in AD. Antioxidant treatments may be beneficial in restoring proNGF signalling and axonal transport and reducing basal forebrain neurodegeneration and related deficits in cognitive function.

scholarly journals Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Mallory Gough ◽  
Catherine Parr-Sturgess ◽  
Edward Parkin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Neuronal Death ◽  
Amyloid Beta Peptide ◽  
Positive Side ◽  
Beta Peptide ◽  
Peptide Metabolism ◽  
The Brain

Alzheimer's disease is a neurodegenerative condition characterized by an accumulation of toxic amyloid beta- (A-)peptides in the brain causing progressive neuronal death. A-peptides are produced by aspartyl proteinase-mediated cleavage of the larger amyloid precursor protein (APP). In contrast to this detrimental “amyloidogenic” form of proteolysis, a range of zinc metalloproteinases can process APP via an alternative “nonamyloidogenic” pathway in which the protein is cleaved within its A region thereby precluding the formation of intact A-peptides. In addition, other members of the zinc metalloproteinase family can degrade preformed A-peptides. As such, the zinc metalloproteinases, collectively, are key to downregulating A generation and enhancing its degradation. It is the role of zinc metalloproteinases in this “positive side of proteolysis in Alzheimer's disease” that is discussed in the current paper.

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