Review of Pharmacotherapeutic Targets in Alzheimer's Disease and Its Management Using Traditional Medicinal Plants.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. While there is currently no cure for AD, several pharmacotherapeutic targets and management strategies have been explored. Additionally, traditional medicinal plants have gained attention for their potential role in AD management.

Dephosphorylation Assay with Recombinant Nil Phosphatase.

The activity of numerous autophagy-related proteins depends on their phosphorylation status, which places importance on understanding the responsible kinases and phosphatases. Great progress has been made in identifying kinases regulating autophagy, but much less is known about the phosphatases counteracting their function. Genetic screens and modern proteomic approaches provide powerful tools to identify candidate phosphatases, but further experiments are required to assign direct roles for candidates.

The growing concern of chlorpyrifos exposures on human and environmental health.

Chlorpyrifos (CP) and its highly electrophilic intermediates are principal toxic metabolites. The active form of CP i.e.

STING controls energy stress-induced autophagy and energy metabolism via STX17.

The stimulator of interferon genes (STING) plays a critical role in innate immunity. Emerging evidence suggests that STING is important for DNA or cGAMP-induced non-canonical autophagy, which is independent of a large part of canonical autophagy machineries. Here, we report that, in the absence of STING, energy stress-induced autophagy is upregulated rather than downregulated.

A phosphoswitch at acinus-serine controls autophagic responses to cadmium exposure and neurodegenerative stress.

Neuronal health depends on quality control functions of autophagy, but mechanisms regulating neuronal autophagy are poorly understood. Previously, we showed that in starvation-independent quality control autophagy is regulated by acinus (acn) and the Cdk5-dependent phosphorylation of its serine (Nandi et al., 2017).

Yorkie Growth-Promoting Activity Is Limited by Atg1-Mediated Phosphorylation.

The expression of multiple growth-promoting genes is coordinated by the transcriptional co-activator Yorkie with its major regulatory input provided by the Hippo-Warts kinase cascade. Here, we identify Atg1/ULK1-mediated phosphorylation of Yorkie as an additional inhibitory input independent of the Hippo-Warts pathway. Two serine residues in Yorkie, S74 and S97, are Atg1/ULK1 consensus target sites and are phosphorylated by ULK1 in vitro, thereby preventing its binding to Scalloped.

Cdk5-mediated Acn/Acinus phosphorylation regulates basal autophagy independently of metabolic stress.

In neurons, autophagy counteracts consequences of aging. It is therefore of interest how basal rates of macroautophagy/autophagy can be controlled independently of metabolic stress. We recently investigated the regulation of basal, starvation-independent autophagy by Acn/Acinus, a multifunctional nuclear protein with proposed roles in apoptosis, alternative RNA splicing, and basal autophagy.

Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in by phosphorylating acinus at serine.

Cdk5 is a post-mitotic kinase with complex roles in maintaining neuronal health. The various mechanisms by which Cdk5 inhibits and promotes neurodegeneration are still poorly understood. Here, we show that in Cdk5 regulates basal autophagy, a key mechanism suppressing neurodegeneration.

Activated Acinus boosts basal autophagy.

Acinus (Acn) is a nuclear protein that participates in the regulation of autophagy. Loss of Acn function prevents autophagy in starving cells. Conversely, Acn activation induces basal autophagy.

Acinus integrates AKT1 and subapoptotic caspase activities to regulate basal autophagy.

How cellular stresses up-regulate autophagy is not fully understood. One potential regulator is the Drosophila melanogaster protein Acinus (Acn), which is necessary for autophagy induction and triggers excess autophagy when overexpressed. We show that cell type-specific regulation of Acn depends on proteolysis by the caspase Dcp-1.

Mechanism of amphotericin B resistance in clinical isolates of Leishmania donovani.

The clinical value of amphotericin B, the mainstay therapy for visceral leishmaniasis in sodium antimony gluconate-nonresponsive zones of Bihar, India, is now threatened by the emergence of acquired drug resistance, and a comprehensive understanding of the underlying mechanisms is the need of the hour. We have selected an amphotericin B-resistant clinical isolate which demonstrated 8-fold-higher 50% lethal doses (LD(50)) than an amphotericin B-sensitive strain to explore the mechanism of amphotericin B resistance. Fluorimetric analysis demonstrated lower anisotropy in the motion of the diphenylhexatriene fluorescent probe in the resistant strain, which indicated a higher fluidity of the membrane for the resistant strain than for the sensitive strain.

Anoikis potential of Entameba histolytica secretory cysteine proteases: evidence of contact independent host cell death.

Mammalian epithelial, endothelial and various other cell types, upon their detachment from the extracellular matrix (ECM) undergo a specialized kind of apoptosis, known as anoikis. Entameba histolytica cysteine proteases have been implicated in degradation of the host ECM, which may induce anoikis in host cells. To explore this hypothesis, supernatant obtained from 2 h in-vitro cultivation of E.

Involvement of thermoplasmaquinone-7 in transplasma membrane electron transport of Entamoeba histolytica trophozoites: a key molecule for future rational chemotherapeutic drug designing.

The quinone composition of the transplasma membrane electron transport chain of parasitic protozoa Entamoeba histolytica was investigated. Purification of quinone from the plasma membrane of E. histolytica and its subsequent structural elucidation revealed the structure of the quinone as a methylmenaquinone-7 (thermoplasmaquinone-7), a napthoquinone.

Hydrogen peroxide induces apoptosis-like death in Entamoeba histolytica trophozoites.

Programmed cell death (PCD) is an essential process in the growth and development of multicellular organisms. However, accumulating evidence indicates that unicellular eukaryotes can also undergo PCD with apoptosis-like features. This study demonstrates that after exposure to 0.

The 29-kilodalton thiol-dependent peroxidase of Entamoeba histolytica is a factor involved in pathogenesis and survival of the parasite during oxidative stress.

The 29-kDa surface antigen (thiol-dependent peroxidase; Eh29) of Entamoeba histolytica exhibits peroxidative and protective antioxidant activities. During tissue invasion, the trophozoites are exposed to oxidative stress and need to deal with highly toxic reactive oxygen species (ROS). In this investigation, attempts have been made to understand the role of the 29-kDa peroxidase gene in parasite survival and pathogenesis.

Preliminary evidence on existence of transplasma membrane electron transport in Entamoeba histolytica trophozoites: a key mechanism for maintaining optimal redox balance.

Entamoeba histolytica, an amitochondriate parasitic protist, was demonstrated to be capable of reducing the oxidized form of alpha-lipoic acid, a non permeable electron acceptor outside the plasma membrane. This transmembrane reduction of non permeable electron acceptors with redox potentials ranging from -290 mV to +360 mV takes place at neutral pH. The transmembrane reduction of non permeable electron acceptors was not inhibited by mitochondrial electron transport inhibitors such as antimycin A, rotenone, cyanide and azide.