scholarly journals Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease

2018 ◽  
Vol 61 (3) ◽  
pp. 843-866 ◽  
Author(s):  
P. Hemachandra Reddy ◽  
Maria Manczak ◽  
Xiangling Yin ◽  
Mary Catherine Grady ◽  
Andrew Mitchell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Protective Effects

scholarly journals Protective effects of a natural product, curcumin, against amyloid β induced mitochondrial and synaptic toxicities in Alzheimer's disease

2016 ◽  
Vol 64 (8) ◽  
pp. 1220-1234 ◽  
Author(s):  
P Hemachandra Reddy ◽  
Maria Manczak ◽  
Xiangling Yin ◽  
Mary Catharine Grady ◽  
Andrew Mitchell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Viability ◽  
Natural Product ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Amyloid Β ◽  
Synaptic Activity ◽  
Protective Effects

The purpose of our study was to investigate the protective effects of a natural product—‘curcumin’— in Alzheimer's disease (AD)-like neurons. Although much research has been done in AD, very little has been reported on the effects of curcumin on mitochondrial biogenesis, dynamics, function and synaptic activities. Therefore, the present study investigated the protective effects against amyloid β (Aβ) induced mitochondrial and synaptic toxicities. Using human neuroblastoma (SHSY5Y) cells, curcumin and Aβ, we studied the protective effects of curcumin against Aβ. Further, we also studied preventive (curcumin+Aβ) and intervention (Aβ+curcumin) effects of curcumin against Aβ in SHSY5Y cells. Using real time RT-PCR, immunoblotting and immunofluorescence analysis, we measured mRNA and protein levels of mitochondrial dynamics, mitochondrial biogenesis and synaptic genes. We also assessed mitochondrial function by measuring hydrogen peroxide, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP. Cell viability was studied using the MTT assay. Aβ was found to impair mitochondrial dynamics, reduce mitochondrial biogenesis and decrease synaptic activity and mitochondrial function. In contrast, curcumin enhanced mitochondrial fusion activity and reduced fission machinery, and increased biogenesis and synaptic proteins. Mitochondrial function and cell viability were elevated in curcumin treated cells. Interestingly, curcumin pre- and post-treated cells incubated with Aβ showed reduced mitochondrial dysfunction, and maintained cell viability and mitochondrial dynamics, mitochondrial biogenesis and synaptic activity. Further, the protective effects of curcumin were stronger in pretreated SHSY5Y cells than in post-treated cells, indicating that curcumin works better in prevention than treatment in AD-like neurons. Our findings suggest that curcumin is a promising drug molecule to treat AD patients.

scholarly journals Pre-Clinical Neuroprotective Evidences and Plausible Mechanisms of Sulforaphane in Alzheimer’s Disease

2021 ◽  
Vol 22 (6) ◽  
pp. 2929
Author(s):  
Jiyoung Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Autism Spectrum ◽  
Cruciferous Vegetables ◽  
Related Factor ◽  
Protective Effects ◽  
Carcinogenic Agent ◽  
Clinical Biomarkers

Sulforaphane, a potent dietary bioactive agent obtainable from cruciferous vegetables, has been extensively studied for its effects in disease prevention and therapy. Sulforaphane potently induces transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated expression of detoxification, anti-oxidation, and immune system-modulating enzymes, and possibly acts as an anti-carcinogenic agent. Several clinical trials are in progress to study the effect of diverse types of cruciferous vegetables and sulforaphane on prostate cancer, breast cancer, lung cancer, atopic asthmatics, skin aging, dermatitis, obesity, etc. Recently, the protective effects of sulforaphane on brain health were also considerably studied, where the studies have further extended to several neurological diseases, including Alzheimer’s disease (AD), Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, multiple sclerosis, autism spectrum disorder, and schizophrenia. Animal and cell studies that employ sulforaphane against memory impairment and AD-related pre-clinical biomarkers on amyloid-β, tau, inflammation, oxidative stress, and neurodegeneration are summarized, and plausible neuroprotective mechanisms of sulforaphane to help prevent AD are discussed. The increase in pre-clinical evidences consistently suggests that sulforaphane has a multi-faceted neuroprotective effect on AD pathophysiology. The anti-AD-like evidence of sulforaphane seen in cells and animals indicates the need to pursue sulforaphane research for relevant biomarkers in AD pre-symptomatic populations.

scholarly journals Intracellular ways of development of Alzheimer's disease against the background of herpes viral infections (literature review)

2021 ◽  
Vol 26 (1) ◽  
pp. 40-46
Author(s):  
S.S. Ostrovska ◽  
V.F. Shatorna ◽  
E.O. Liholetov
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
The Body ◽  
Tau Proteins ◽  
Postmortem Brain ◽  
Amyloid Β Peptide ◽  
Protective Effects ◽  
Increased Risk ◽  
The Brain

The concept of the viral etiology of Alzheimer's disease (AD) was first proposed in 1982. Its author MJ Ball suggested that the herpes simplex virus (HSV1) may be involved in the pathogenesis of AD, finding that the areas of the brain damaged in acute herpetic encephalitis are the same as those that are affected in AD, and those who survived usually suffer from memory loss and other cognitive impairment typical of AD. Subsequently, in all postmortem brain samples (temporal, frontal, and hippocampal) viral sequences of the viral thymidinekinase gene were found in a high proportion (70-100%) both in AD and in elderly people without it, while in young people and children the virus was found in very low proportions, so it was suggested that HSV1 comes from the peripheral ganglia, where the virus can remain inactive for many years, then enters the brain at an older age due to a decrease in the activity of the immune system. The increased risk of AD is associated with the presence of HSV1 in the brain and the carriage of a specific genetic factor – allele-ε4 of the apolipoprotein E4 gene (APOE-ε4). By themselves, neither HSV1 nor the APOE-ɛ4 allele were found as risk factors for the development of AD but their combination increased the risk of AD development by 12 times and made up 60% in patients with AD. The phenomena involved in the pathophysiology of AD are neurodegenerative changes that occur as a result of fibrillation and deposition of amyloid-β-peptide (Aβ) and neurofibrillary tangles – accumulations of aggregated phosphorylated tau-proteins (P-tau), leading to brain atrophy due to neuronal death. Traditionally, Aβ has been characterized as a catabolic by-product. However, it has recently been shown that Aβ-peptide has antiviral activity and protective effects against HSV infections in the brain. А 16-year study in Thailand with more than 33,000 patients showed that long-term use of antiherpetic drugs reduces the risk of dementia, including AD patients infected with HSV1. Patients with HSV1 infection who received antiherpetic drugs showed a lower risk of all types of dementia compared with the group without these drugs. Their positive effect on stopping the accumulation of amyloid beta and tau protein in the body has been confirmed. In this regard, it is assumed that vaccination against HSV1 may be useful not only for treatment, but also for the prevention of AD.

scholarly journals BMI1 is associated with CS8F amyloid-β and rates of cognitive decline in Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jun Pyo Kim ◽  
Bo-Hyun Kim ◽  
Paula J. Bice ◽  
Sang Won Seo ◽  
David A. Bennett ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Association Analysis ◽  
Amyloid Β ◽  
Minor Allele ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Minor Alleles

Abstract Background Accumulating evidence suggests that BMI1 confers protective effects against Alzheimer’s disease (AD). However, the mechanism remains elusive. Based on recent pathophysiological evidence, we sought for the first time to identify genetic variants in BMI1 as associated with AD biomarkers, including amyloid-β. Methods We used genetic, longitudinal cognition, and cerebrospinal fluid (CSF) biomarker data from participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort (N = 1565). First, we performed a gene-based association analysis of common single nucleotide polymorphisms (SNPs) (minor allele frequency (MAF) > 5%) located within ± 20 kb of the gene boundary of BMI1, an optimal width for including potential regulatory SNPs in the 5′ and 3′ untranslated regions (UTR) of BMI1, with CSF Aβ1-42 levels. Second, we performed cross-sectional and longitudinal association analyses of SNPs in BMI1 with cognitive performance using linear and mixed-effects models. We replicated association of SNPs in BMI1 with cognitive performance in an independent cohort (N=1084), Religious Orders Study and the Rush Memory and Aging Project (ROS/MAP). Results Gene-based genetic association analysis showed that BMI1 was significantly associated with CSF Aβ1-42 levels after adjusting for multiple testing using permutation (permutation-corrected p value=0.005). rs17415557 in BMI1 showed the most significant association with CSF Aβ1-42 levels. Participants with minor alleles of rs17415557 have increased CSF Aβ1-42 levels compared to those with no minor alleles. Further analysis identified and replicated the minor allele of rs17415557 as being significantly associated with slower cognitive decline rates in AD. Conclusions Our findings provide fundamental evidence that BMI1 rs17415557 may serve as a protective mechanism related to AD pathogenesis, which supports the results of previous studies linking BMI1 to protection against AD.

scholarly journals Protective effects of BACE1 inhibitory ligand molecules against amyloid beta-induced synaptic and mitochondrial toxicities in Alzheimer’s disease

2019 ◽  
Vol 29 (1) ◽  
pp. 49-69 ◽  
Author(s):  
Jangampalli Adi Pradeepkiran ◽  
Arubala P Reddy ◽  
Xiangling Yin ◽  
Maria Manczak ◽  
P Hemachandra Reddy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Amyloid Β ◽  
Synaptic Activity ◽  
Brain State ◽  
Potential Candidate ◽  
Protective Effects ◽  
App Processing

Abstract Amyloid-β (Aβ) peptides are the major drivers of Alzheimer’s disease (AD) pathogenesis, and are formed by successive cleavage of the amyloid precursor protein (APP) by the beta and gamma secretases. Mounting evidence suggests that Aβ and mitochondrial structural and functional abnormalities are critically involved in the loss of synapses and cognitive decline, in patients with AD. In AD brain, state the sequential proteolytic cleavage of APP by beta secretase 1 enzyme (BACE1) and γ-secretase leads to the production and release of Aβ40 and 42. BACE1 expression and activity increased in the brains of AD patients. Structurally, β-secretase has a very large binding site (1000 Å) with fewer hydrophobic domains that makes a challenge to identify the specific targets/binding sites of BACE1. In the present study, we constructed a BACE1 pharmacophore with pepstatin and screened through molecular docking studies. We found one potential candidate (referred as ligand 1) that binds to the key catalytic residues of BACE1 and predicts to inhibit abnormal APP processing and reduce Aβ levels in AD neurons. Using biochemical, molecular, transmission electron microscopy, immunoblotting and immunofluorescence analyses, we studied the protective effects of ligand 1 against Aβ-induced synaptic and mitochondrial toxicities in mouse neuroblastoma (N2a) cells that express mutant APP. We found interaction between ligand 1 and BACE1 and this interaction decreased BACE1 activity, Aβ40 and 42 levels. We also found increased mitochondrial biogenesis, mitochondrial fusion and synaptic activity and reduced mitochondrial fission in ligand 1-treated mutant APP cells. Based on these results, we cautiously conclude that ligand 1 reduces Aβ-induced mitochondrial and synaptic toxicities, and maintains mitochondrial dynamics and neuronal function in AD.

scholarly journals Celastrol Attenuates Learning and Memory Deficits in an Alzheimer’s Disease Rat Model

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yao Xiao ◽  
Xifeng Wang ◽  
Siyi Wang ◽  
Jun Li ◽  
Xueyu Xu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Rat Model ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Synaptic Function ◽  
Inflammatory Factors ◽  
Protective Effects ◽  
Pentacyclic Triterpene

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder that is associated with learning, memory, and cognitive deficits. Neuroinflammation and synapse loss are involved in the pathology of AD. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Celastrol (CEL) is a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F that has been shown to enhance cell viability and inhibit amyloid-β production induced by lipopolysaccharides in vitro. In the present study, the protective effect of CEL on Aβ25-35-induced rat model of AD was assessed. Our results showed that CEL administration at a dose of 2 mg/kg/day improved spatial memory in the Morris water maze. Further biochemical analysis showed that CEL treatment of intrahippocampal Aβ25-35-microinjected rats attenuated hippocampal NF-κB activity; inhibited proinflammatory markers, namely, IL-1β, IL-6, and TNF-α; and upregulated anti-inflammatory factors, such as IL-4 and IL-10. Furthermore, CEL upregulated hippocampal neurexin-1β, neuroligin-1, CA1, and PSD95 expression levels, which may improve synaptic function. Simultaneously, CEL also increased glucose metabolism in Aβ25-35-microinjected rats. In conclusion, CEL could exert protective effects against learning and memory decline induced by intrahippocampal Aβ25-35 through anti-inflammation, promote synaptic development, and maintain hippocampal energy metabolism.

Amyloid β-peptide and Alzheimer's disease

2014 ◽  
Vol 56 ◽  
pp. 99-110 ◽  
Author(s):  
David Allsop ◽  
Jennifer Mayes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Strong Support ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
Sequence Of Events ◽  
Aβ Amyloid ◽  
Amyloid Cascade

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.

Minimalistic Design Approach for Multi-Reactivity against Free Radicals and Metal-Free and Metal-Bound Amyloid-β Peptides: Redox-Based Substitutions of Benzene

2019 ◽  
Author(s):  
Mingeun Kim ◽  
Juhye Kang ◽  
Misun Lee ◽  
Jiyeon Han ◽  
Geewoo Nam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radicals ◽  
Amyloid Β ◽  
Design Strategy ◽  
Design Approach ◽  
Metal Free

We report a minimalistic redox-based design strategy for engineering compact molecules based on the simplest aromatic framework, benzene, with multi-reactivity against free radicals, metal-free amyloid-β, and metal-bound amyloid-β, implicated in the most common form of dementia, Alzheimer’s disease.

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