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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.

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.

Here, based on the identification of androgapholide as a potential therapeutic treatment against cancer, Alzheimer's disease, diabetes, and multiple sclerosis, due to its ability to inhibit a signaling pathway in immune system function, the authors sought ways to optimize the natural product human systems by manipulating its chemical structure. Through the semisynthesis of a natural product along with computational studies, the authors developed an understanding of the kinetic mechanisms of andrographolide and semisynthetic analogs in the context of Michael additions.

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 Aβ_1-40 peptide levels in human neuroblastoma cells. Their results suggest that bugleweed may have the potential to reduce Aβ_1-40 levels through its anti-inflammatory properties.

Here, the authors investigated the role of nonpharmacological interventions in preventing or delaying cognitive impairment in individuals with and without dementia. By using a retrospective case-control study of 22 participants across two senior centers in San Diego, they found no significant differences in self-reported activities. However, they found that their results reflected activity rather than the activity itself, suggesting the need for an alternative type of study.

Kalirin is a guanine nucleotide exchange factor (GEF) for the GTPase RAC1, linked to schizophrenia and Alzheimer’s Disease. It plays a crucial role in synaptic plasticity by regulating dendritic spine formation and actin cytoskeleton remodeling, which are essential for creating new synapses. Authors developed two novel compounds targeting kalirin, confirming that predictive modeling can indicate biological activity.

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder in the U.S., second only to Alzheimer’s disease. Current diagnostic methods are often inefficient and dependent on clinical exams. This study explored using machine and deep learning to enhance PD diagnosis by analyzing spiral drawings affected by hand tremors, a common PD symptom.

The authors employ computational protein design to identify a mini-protein with the potential to enhance binding of the tight junction protein, claudin-5, at the blood-blood barrier with therapeutic potential for neurodegenerative diseases.

The authors looked at whether they could induce the formation of new neurons from astrocytes via the upregulation of a microRNA (miR-124a). They found that upregulation of miR-124a started transdifferentiation of neurons, but was not enough to lead to full conversion of astrocytes to neurons.

PDE8, a type of phosphodiesterase (PDE), is proven to be crucial in various cellular activities and physiological activities by influencing second messenger systems. It is involved in a wide range of diseases, including Alzheimer’s disease and various heart diseases. However, there is limited information about PDE8 selective inhibitors. This work aimed to improve the solubility and yield of PDE8 in the supernatant by exploring suitable culture conditions, including temperatures and different additives.