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Expression of Anti-Neurodegeneration Genes in Mutant Caenorhabditis elegans Using CRISPR-Cas9 Improves Behavior Associated With Alzheimer’s Disease

Mishra et al. | Sep 14, 2019

Expression of Anti-Neurodegeneration Genes in Mutant <em>Caenorhabditis elegans</em> Using CRISPR-Cas9 Improves Behavior Associated With Alzheimer’s Disease

Alzheimer's disease is one of the leading causes of death in the United States and is characterized by neurodegeneration. Mishra et al. wanted to understand the role of two transport proteins, LRP1 and AQP4, in the neurodegeneration of Alzheimer's disease. They used a model organism for Alzheimer's disease, the nematode C. elegans, and genetic engineering to look at whether they would see a decrease in neurodegeneration if they increased the amount of these two transport proteins. They found that the best improvements were caused by increased expression of both transport proteins, with smaller improvements when just one of the proteins is overly expressed. Their work has important implications for how we understand neurodegeneration in Alzheimer's disease and what we can do to slow or prevent the progression of the disease.

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Using the COmplex PAthway SImulator, Stage Analysis, and Chemical Kinetics to Develop a Novel Solution to Lower Tau Concentrations in Alzheimer’s Disease

Carroll et al. | Sep 28, 2020

Using the COmplex PAthway SImulator, Stage Analysis, and Chemical Kinetics to Develop a Novel Solution to Lower Tau Concentrations in Alzheimer’s Disease

In this study, the authors ask whether a Tau immunotherapy treatment, Hsp70 protein treatment, or dual treatment approach of both the Tau imunotherapy treatment and Hsp70 protein treatment leads to a greater reduction in Tau protein concentration in Alzheimer's disease. Overall, they conclude that the effectiveness of the treatment ultimately relies on the stage of Alzheimer’s.

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Effects on Learning and Memory of a Mutation in Dα7: A D. melanogaster Homolog of Alzheimer's Related Gene for nAChR α7

Sanyal et al. | Oct 01, 2019

Effects on Learning and Memory of a Mutation in Dα7: A <em>D. melanogaster</em> Homolog of Alzheimer's Related Gene for nAChR α7

Alzheimer's disease (AD) involves the reduction of cholinergic activity due to a decrease in neuronal levels of nAChR α7. In this work, Sanyal and Cuellar-Ortiz explore the role of the nAChR α7 in learning and memory retention, using Drosophila melanogaster as a model organism. The performance of mutant flies (PΔEY6) was analyzed in locomotive and olfactory-memory retention tests in comparison to wild type (WT) flies and an Alzheimer's disease model Arc-42 (Aβ-42). Their results suggest that the lack of the D. melanogaster-nAChR causes learning, memory, and locomotion impairments, similar to those observed in Alzheimer's models Arc-42.

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A novel approach for early detection of Alzheimer’s disease using deep neural networks with magnetic resonance imaging

Ganesh et al. | Mar 20, 2022

A novel approach for early detection of Alzheimer’s disease using deep neural networks with magnetic resonance imaging

In the battle against Alzheimer's disease, early detection is critical to mitigating symptoms in patients. Here, the authors use a collection of MRI scans, layering with deep learning computer modeling, to investigate early stages of AD which can be hard to catch by human eye. Their model is successful, able to outperform previous models, and detected regions of interest in the brain for further consideration.

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A Novel Alzheimer's Disease Therapeutic Model: Attenuating Hyperphosphorylated Tau and Amyloid β (Aβ) Aggregates by Characterizing Antioxidative, Anti-Inflammatory, and Neuroprotective Properties of Natural Extracts

Pokkunuri et al. | Jul 25, 2022

A Novel Alzheimer's Disease Therapeutic Model: Attenuating Hyperphosphorylated Tau and Amyloid β (Aβ) Aggregates by Characterizing Antioxidative, Anti-Inflammatory, and Neuroprotective Properties of Natural Extracts

Oxidative damage and neuro-inflammation were the key pathways implicated in the pathogenesis of Alzheimer’s disease. In this study, 30 natural extracts from plant roots and leaves with extensive anti-inflammatory and anti-oxidative properties were consumed by Drosophila melanogaster. Several assays were performed to evaluate the efficacy of these combinational extracts on delaying the progression of Alzheimer’s disease. The experimental group showed increased motor activity, improved associative memory, and decreased lifespan decline relative to the control group.

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Potential Multifunctional Agents for Dual Therapy of Age-Related and Associated Diseases: Alzheimer’s Disease and Type 2 Diabetes Mellitus

Kumar et al. | Nov 13, 2019

Potential Multifunctional Agents for Dual Therapy of Age-Related and Associated Diseases: Alzheimer’s Disease and Type 2 Diabetes Mellitus

Studies show an age-related link between Alzheimer’s Disease and Type 2 Diabetes Mellitus with oxidative stress a characteristic of both. Here, methanolic fractionations and extracts of four Ayurvedic plants were assessed for their protective abilities using a number of in vitro assays. Extracts inhibited oxidative stress and reduced activity of key enzymes involved in the pathogenesis of both diseases in neuroblastoma cells.

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Assessing CDK5 as a Nanomotor for Chemotactic Drug Delivery

Jiang et al. | Sep 08, 2022

Assessing CDK5 as a Nanomotor for Chemotactic Drug Delivery

Enzyme chemotaxis is a thermodynamic phenomenon in which enzymes move along a substrate concentration gradient towards regions with higher substrate concentrations and can be used to steer nanovehicles towards targets along natural substrate concentrations. In patients with Alzheimer’s disease, a gradient of tau protein forms in the bloodstream. Tau protein is a substrate of the enzyme CDK5, which catalyzes the phosphorylation of tau protein and can travel using chemotaxis along tau protein gradients to increasing concentrations of tau and amyloid-beta proteins. The authors hypothesized that CDK5 would be able to overcome these barriers of Brownian motion and developed a quantitative model using Michaelis-Menten kinetics to define the necessary parameters to confirm and characterize CDK5’s chemotactic behavior to establish its utility in drug delivery and other applications.

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Herbal Extracts Alter Amyloid Beta Levels in SH-SY5Y Neuroblastoma Cells

Xu et al. | Feb 25, 2020

Herbal Extracts Alter Amyloid Beta Levels in SH-SY5Y Neuroblastoma Cells

Alzheimer’s disease (AD) is a type of dementia that affects more than 5.5 million Americans, and there are no approved treatments that can delay the advancement of the disease. In this work, Xu and Mitchell test the effects of various herbal extracts (bugleweed, hops, sassafras, and white camphor) on Aβ1-40 peptide levels in human neuroblastoma cells. Their results suggest that bugleweed may have the potential to reduce Aβ1-40 levels through its anti-inflammatory properties.

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Modular mimics of neuroactive alkaloids - design, synthesis, and cholinesterase inhibitory activity of rivastigmine analogs

Yu et al. | Sep 12, 2022

Modular mimics of neuroactive alkaloids - design, synthesis, and cholinesterase inhibitory activity of rivastigmine analogs

Naturally occurring neuroactive alkaloids are often studied for their potential to treat Neurological diseases. This team of students study Rivastigmine, a potent cholinesterase inhibitor that is a synthetic analog of physostigmine, which comes from the Calabar bean plant Physostigma venenosum. By comparing the effects of optimized synthetic analogs to the naturally occurring alkaloid, they determine the most favorable analog for inhibition of acetylcholinesterase (AChE), the enzyme that breaks down the neurotransmitter acetylcholine (ACh) to terminate neuronal transmission and signaling between synapses.

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Efficacy of Mass Spectrometry Versus 1H Nuclear Magnetic Resonance With Respect to Denaturant Dependent Hydrogen-Deuterium Exchange in Protein Studies

Chenna et al. | Jan 22, 2020

Efficacy of Mass Spectrometry Versus 1H Nuclear Magnetic Resonance With Respect to Denaturant Dependent Hydrogen-Deuterium Exchange in Protein Studies

The misfolding of proteins leads to numerous diseases including Akzheimer’s, Parkinson’s and Type II Diabetes. Understanding of exactly how proteins fold is crucial for many medical advancements. Chenna and Englander addressed this problem by measuring the rate of hydrogen-deuterium exchange within proteins exposed to deuterium oxide in order to further elucidate the process of protein folding. Here, mass spectrometry was used to measure exchange in Cytochrome c and was compared to archived 1H NMR data.

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