Revisiting the role of phospholipases in alzheimer's: crosstalk with processed food.

Phospholipases such as phospholipase-A, phospholipase-B, phospholipase-C and phospholipase-D are important functional enzymes of the cell membrane responsible for a variety of functions such as signal transduction, production of lipid mediators, metabolite digestion and playing a pathological role in central nervous system diseases. Phospholipases have shown an association with Alzheimer's disease and these enzymes have found a correlation with several metabolic pathways that can lead to the activation of inflammatory signals via astrocytes and microglial cells. We also highlighted unhealthy practices like smoking and consuming processed foods, rich in nitroso compounds and phosphatidic acid, which contribute to neuronal damage in AD through phospholipases. A few therapeutic approaches such as the use of inhibitors of phospholipase-D,phospholipase A2 as well as autophagy-mediated inhibition have been discussed to control the onset of AD. This paper serves as a crosstalk between phospholipases and their role in neurodegenerative pathways as well as their influence on other biomolecules of lipid membranes, which are acquired through unhealthy diets and possible methods to treat these anomalies occurring due to their metabolic disorder involving phospholipases acting as major signaling molecules.

Role of calcium dysregulation in Alzheimer's disease and its therapeutic implications.

The increasing incidence of Alzheimer's disease (AD) coupled with the lack of therapeutics to address the underlying pathology of the disease has necessitated the need for exploring newer targets. Calcium dysregulation represents a relatively newer target associated with AD. Ca+2 serves as an important cellular messenger in neurons. The concentration of the Ca+2 ion needs to be regulated at optimal concentrations intracellularly for normal functioning of the neurons. This is achieved with the help of mitochondria, endoplasmic reticulum, and neuronal plasma membrane channel proteins. Disruption in normal calcium homeostasis can induce formation of amyloid beta plaques, accumulation of neurofibrillary tangles, and dysfunction of synaptic plasticity, which in turn can affect calcium homeostasis further, thus forming a vicious cycle. Hence, understanding calcium dysregulation can prove to be a key to develop newer therapeutics. This review provides detailed account of physiology of calcium homeostasis and its dysregulation associated with AD. Further, with an understanding of various receptors and organelles involved in these pathways, the review also discusses various calcium channel blockers explored in AD hand in hand with some multitarget molecules addressing calcium as one of the targets.

Tackling SARS-CoV-2: proposed targets and repurposed drugs.

The SARS-CoV-2 pandemic, declared as a global health emergency by the WHO in February 2020, has currently infected more than 6 million people with fatalities near 371,000 and increasing exponentially, in absence of vaccines and drugs. The pathogenesis of SARS-CoV-2 is still being elucidated. Identifying potential targets and repurposing drugs as therapeutic options is the need of the hour. In this review, we focus on potential druggable targets and suitable therapeutics, currently being explored in clinical trials, to treat SARS-CoV-2 infection. A brief understanding of the complex interactions of both viral as well as host targets, and the possible repurposed drug candidates are described with an emphasis on understanding the mechanisms at the molecular level.

Comparison of ICD implantation in obese and nonobese patients.

BACKGROUND: Implantable defibrillator (ICD) therapy improves mortality in patients at risk for sudden cardiac death. Obese patients pose challenges during ICD implantation and may have an increased risk of procedure-related complications. The comparison of acute procedural success and safety of ICD implantation in obese and nonobese patients has not been previously reported. METHODS: A total of 181 patients underwent ICD implantation at a single institution. Obesity was defined as a body mass index (BMI) greater than or equal to 30 kg/m(2) . Acute safety and efficacy data were collected and analyzed from a prospectively maintained database, with retrospective chart review, as required. RESULTS: Among the 181 patients, 58 (32.0%) were obese. Mean BMI was 36.7 ± 6.3 kg/m(2) among obese patients and was 24.6 ± 3.1 kg/m(2) among nonobese patients (P < 0.001). Successful ICD implantation occurred in 58 of 58 (100%) obese patients and 122 of 123 (99.2%) nonobese patients (P = 1.0). A complication was observed in three of 58 (5.2%) obese patients and in seven of 123 (5.7%) nonobese patients (P = 1.0). Similarly, there was no difference in acute procedural success and safety in patients receiving a cardiac resynchronization therapy (CRT)-ICD. CONCLUSIONS: Acute success and safety of ICD implantation is similar in both obese and nonobese patients. This finding extended to patients treated with a CRT-ICD and among patients with extreme obesity. Obesity should probably not be a factor in determining whether a patient is a candidate for ICD implantation.