bims-metalz 2024-05-26 papers

Issue of 2024–05–26
seven papers selected by
Mikaila Chetty, Goa University

MicroPubl Biol. 2024 ;2024

Exposure to an aversive odor alters Caenorhabditis elegans physiology.

Joyobrata Sarkar, Kshitij Vashisth, Anubhuti Dixit.

Perception of external cues is important for enhancing the fitness and survival of animals. However, the role of odor perception in regulation of longevity and health is incompletely defined. Here, we show that the exposure to an aversive odor 2-nonanone reduces life span, brood size, feeding rate, and increases lipid storage in worms. These effects are restored to normal levels in mutant worms lacking functional olfactory AWB neurons, suggesting a potential role of odor perception in the regulation of animal physiology and longevity.

DOI: https://doi.org/10.17912/micropub.biology.001198

Phytomedicine. 2024 Apr 27. pii: S0944-7113(24)00324-6. [Epub ahead of print]129 155665

Anti-aging effects of medicinal plants and their rapid screening using the nematode Caenorhabditis elegans.

Xiaodan Chen, Faranak Bahramimehr, Nasim Shahhamzehei, Huangjie Fu, Siyi Lin, Hanxiao Wang, Changyu Li, Thomas Efferth, Chunlan Hong.

BACKGROUND: Aging is the primary risk factor of most chronic diseases in humans, including cardiovascular diseases, osteoporosis and neurodegenerative diseases, which extensively damage the quality of life for elderly individuals. Aging is a multifaceted process with numerous factors affecting it. Efficient model organisms are essential for the research and development of anti-aging agents, particularly when investigating pharmacological mechanisms are needed.
PURPOSE: This review discusses the application of Caenorhabditis elegans for studying aging and its related signaling pathways, and presents an overview of studies exploring the mechanism and screening of anti-aging agents in C. elegans. Additionally, the review summarizes related clinical trials of anti-aging agents to inspire the development of new medications.
METHOD: Literature was searched, analyzed, and collected using PubMed, Web of Science, and Science Direct. The search terms used were "anti-aging", "medicinal plants", "synthetic compounds", "C. elegans", "signal pathway", etc. Several combinations of these keywords were used. Studies conducted in C. elegans or humans were included. Articles were excluded, if they were on studies conducted in silico or in vitro or could not offer effective data.
RESULTS: Four compounds mainly derived through synthesis (metformin, rapamycin, nicotinamide mononucleotide, alpha-ketoglutarate) and four active ingredients chiefly obtained from plants (resveratrol, quercetin, Astragalus polysaccharide, ginsenosides) are introduced emphatically. These compounds and active ingredients exhibit potential anti-aging effects in preclinical and clinical studies. The screening of these anti-aging agents and the investigation of their pharmacological mechanisms can benefit from the use of C. elegans.
CONCLUSION: Medicinal plants provide valuable resource for the treatment of diseases. A wide source of raw materials for the particular plant medicinal compounds having anti-aging effects meet diverse pharmaceutical requirements, such as immunomodulatory, anti-inflammation and alleviating oxidative stress. C. elegans possesses advantages in scientific research including short life cycle, small size, easy maintenance, genetic tractability and conserved biological processes related to aging. C. elegans can be used for the efficient and rapid evaluation of compounds with the potential to slow down aging.

Keywords: Anti-aging; Caenorhabditis elegans; Medicinal plants; Signal pathway

DOI: https://doi.org/10.1016/j.phymed.2024.155665

MicroPubl Biol. 2024 ;2024

ggbulksurv: An R package for easy Drosophila and C. elegans survival analysis.

Qian Hui Tan, Nathan Harmston, Nicholas S Tolwinski.

Lifespan studies on fast-aging model organisms like C.elegans and D.melanogaster are conducted with multiple organisms per vial. Lifespan data results in a "one row, multiple individuals" format, which is incompatible with R packages that require a "one row, one individual" format. We present ggbulksurv , an R package for user-friendly survival analysis and highlight three key features. (1) pivot_prism converts data for PRISM, allowing biologists to plot survival curves without manually expanding each observation. (2) run_bulksurv() takes in a "one row, multiple individuals" table and plots a customizable survival curve. (3) Advanced users who require custom survival objects can specify a custom formula, facilitating complex survival analysis. We provide a time saving solution for lifespan data analysis.

DOI: https://doi.org/10.17912/micropub.biology.001060

Adv Mater. 2024 May 22. e2314354

Bio-Nano Toolbox for Precision Alzheimer's Disease Gene Therapy.

Yang Liu, Xue Xia, Meng Zheng, Bingyang Shi.

Alzheimer's disease (AD) is the most burdensome aging-associated neurodegenerative disorder, and its treatment encounters numerous failures during drug development. Although there are newly approved in-market β-amyloid targeting antibody solutions, pathological heterogeneity among patient populations still challenges the treatment outcome. Emerging advances in gene therapies offer opportunities for more precise personalized medicine; while, major obstacles including the pathological heterogeneity among patient populations, the puzzled mechanism for druggable target development, and the precision delivery of functional therapeutic elements across the blood-brain barrier remain and limit the use of gene therapy for central neuronal diseases. Aiming for "precision delivery" challenges, nanomedicine provides versatile platforms that may overcome the targeted delivery challenges for AD gene therapy. In this perspective, to picture a toolbox for AD gene therapy strategy development, the most recent advances from benchtop to clinics are highlighted, possibly available gene therapy targets, tools, and delivery platforms are outlined, their challenges as well as rational design elements are addressed, and perspectives in this promising research field are discussed.

Keywords: Alzheimer's disease; blood–brain barrier; drug delivery; gene therapy; nanoparticles

DOI: https://doi.org/10.1002/adma.202314354

Biomedicines. 2024 May 15. pii: 1097. [Epub ahead of print]12(5):

Molecular Role of Protein Phosphatases in Alzheimer's and Other Neurodegenerative Diseases.

Mubashir Hassan, Muhammad Yasir, Saba Shahzadi, Wanjoo Chun, Andrzej Kloczkowski.

Alzheimer's disease (AD) is distinguished by the gradual loss of cognitive function, which is associated with neuronal loss and death. Accumulating evidence supports that protein phosphatases (PPs; PP1, PP2A, PP2B, PP4, PP5, PP6, and PP7) are directly linked with amyloid beta (Aβ) as well as the formation of the neurofibrillary tangles (NFTs) causing AD. Published data reported lower PP1 and PP2A activity in both gray and white matters in AD brains than in the controls, which clearly shows that dysfunctional phosphatases play a significant role in AD. Moreover, PP2A is also a major causing factor of AD through the deregulation of the tau protein. Here, we review recent advances on the role of protein phosphatases in the pathology of AD and other neurodegenerative diseases. A better understanding of this problem may lead to the development of phosphatase-targeted therapies for neurodegenerative disorders in the near future.

Keywords: Alzheimer’s disease; amyloid beta; neurodegenerative diseases; protein phosphatase; tau protein

DOI: https://doi.org/10.3390/biomedicines12051097

ACS Chem Neurosci. 2024 May 20.

Amyloid Mimicking Assemblies Formed by Glutamine, Glutamic Acid, and Aspartic Acid.

Ankita Jaiswal, Monisha Patel, Anam Naseer, Simran Kumari, Neeraja Revi, Aravind Rengan, Alok Jain, Aamir Nazir, Nidhi Gour, Sandeep Verma.

The aggregation of amino acids into amyloid-like structures is a critical phenomenon for understanding the pathophysiology of various diseases, including inborn errors of metabolism (IEMs) associated with amino acid imbalances. Previous studies have primarily focused on self-assembly of aromatic amino acids, leading to a limited understanding of nonaromatic, polar amino acids in this context. To bridge this gap, our study investigates the self-assembly and aggregation behavior of specific nonaromatic charged and uncharged polar amino acids l-glutamine (Gln), l-aspartic acid (Asp), and l-glutamic acid (Glu), which have not been reported widely in the context of amyloid aggregation. Upon aging these amino acids under controlled conditions, we observed the formation of uniform, distinct aggregates, with Gln forming fibrillar gel-like structures and Glu exhibiting fibrous globular morphologies. Computational simulations validated these findings, identifying Gln as the most potent in forming stable aggregates, followed by Glu and Asp. These simulations elucidated the driving forces behind the distinct morphologies and stabilities of the aggregates. Thioflavin T assays were employed to confirm the amyloid-like nature of these aggregates, suggesting their potential cytotoxic impact. To assess toxicity, we performed in vitro studies on neural cell lines and in vivo experiments in Caenorhabditis elegans (C. elegans), which demonstrated measurable cytotoxic effects, corroborated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and heat shock survival assays. Importantly, this study fills a critical gap in our understanding on the role of nonaromatic amino acids in amyloidogenesis and its implications for IEMs. Our findings provide a foundation for future investigations into the mechanisms of diseases associated with amino acid accumulation and offer potential avenues for the development of targeted therapeutic strategies.

Keywords: amyloidogenesis; generic amyloid hypothesis; in-born errors of metabolisms; nonaromatic amino acids; self-assembly

DOI: https://doi.org/10.1021/acschemneuro.4c00082

ACS Appl Bio Mater. 2024 May 20.

Exploring Curcumin-Loaded Lipid-Based Nanomedicine as Efficient Targeted Therapy for Alzheimer's Diseases.

Bahareh Farasati Far, Maryam Safaei, Ali Pourmolaei, Shaghyegh Adibamini, Shiva Shirdel, Shabnam Shirdel, Reza Emadi, Ajeet Kumar Kaushik.

Alzheimer's disease (AD) is a neurological condition currently with 47 million people suffering from it globally. AD might have many reasons such as genetic issues, environmental factors, and Aβ accumulation, which is the biomarker of the disease. Since the primary reason is unknown, there is no targeted treatment at the moment, but ongoing research aims to slow its progression by managing amyloid-beta peptide production rather than symptomatic improvement. Since phytochemicals have been demonstrated to possess antioxidant, anti-inflammatory, and neuroprotective properties, they may target multiple pathological factors and can reduce the risk of the disease. Curcumin, as a phytochemical found in turmeric known for its antioxidant, free radical scavenging properties, and as an antiamyloid in treating AD, has come under investigation. Although its low bioavailability limits its efficacy, a prominent drug delivery system (DDS) is desired to overcome it. Hence, the potency of lipid-based nanoparticles encapsulating curcumin (LNPs-CUR) is considered in this study as a promising DDS. In vivo studies in animal models indicate LNPs-CUR effectively slow amyloid plaque formation, leading to cognitive enhancement and reduced toxicity compared to free CUR. However, a deeper understanding of CUR's pharmacokinetics and safety profile is crucial before LNPs-CUR can be considered as a medicine. Future investigations may explore the combination of NPs with other therapeutic agents to increase their efficacy in AD cases. This review provides the current position of CUR in the AD therapy paradigm, the DDS suggestions for CUR, and the previous research from the point of analytical view focused on the advantages and challenges.

Keywords: Alzheimer’s disease (AD); Amyloid Plaque; Curcumin; Drug Delivery Systems (DDS); Lipid-based nanoparticles (LNPs); Neuroprotection C

DOI: https://doi.org/10.1021/acsabm.4c00112