Parkinson disease (PD) is a progressive neurodegenerative movement disorder characterized by motor and non-motor symptoms due to loss of striatal dopaminergic neurons and disruption of degradation signaling leading to the formation of Lewy bodies (aggregation of α-synuclein). Presently, there are no disease modifying therapy for PD despite improvement in the understanding of the disease pathogenesis. However, the drugs currently used in PD management provide symptomatic relieve for motor symptoms without significant improvement in non-motor complications, thus, a public health burden on caregivers and healthcare systems. There is therefore the need to discover disease modifying therapy with strong potential to halt the disease progression. Recent trend has shown that the dysfunction of lysosomal-autophagy pathway is highly implicated in PD pathology, hence, making autophagy a key player owing to its involvement in degradation and clearance of misfolded α-synuclein (a major hallmark in PD pathology). In this review, we described the current drugs/strategy in the management of PD including targeting the autophagy pathway as a novel approach that could serve as potential intervention for PD management. The discovery of small molecules or natural products capable of enhancing autophagy mechanism could be a promising strategy for PD treatment.
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http://dx.doi.org/10.1515/dmdi-2021-0128 | DOI Listing |
Sci Rep
December 2024
Plum Island Animal Disease Center, Agricultural Research Service, USDA, Greenport, NY, 11944, USA.
For over a century African swine fever (ASF) has been causing outbreaks leading to devastating losses for the swine industry. The current pandemic of ASF has shown no signs of stopping and continues to spread causing outbreaks in additional countries. Currently control relies mostly on culling infected farms, and strict biosecurity procedures.
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December 2024
The University of Trans-Disciplinary Health Sciences and Technology (TDU), 74/2, Post Attur via Yelahanka, Jarakabande Kaval, Bengaluru, 560 064, India.
Triphala is a traditional Ayurvedic herbal formulation composed of three fruits: amla (Phyllanthus emblica), bibhitaki (Terminalia bellerica), and haritaki (Terminalia chebula). Triphala is a potent Ayurvedic remedy that promotes digestion, detoxification, and overall wellness, while also providing antioxidant benefits through its trio of nutrient-rich fruits. In order to elucidate the individual contributions of the three ingredients of Triphala from molecular perspective, the individual ingredients were used for the untargeted LCMS/MS analysis.
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December 2024
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Marine cyclopianes are a family of diterpenoid with novel carbon skeleton and diverse biological activities. Herein, we report our synthetic and chemical proteomics studies of cyclopiane diterpenes which culminate in the asymmetric total synthesis of conidiogenones C, K and 12β-hydroxy conidiogenone C, and identification of Immunity-related GTPase family M protein 1 (IRGM1) as a cellular target. Our asymmetric synthesis commences from Wieland-Miescher ketone and features a sequential intramolecular Pauson-Khand reaction and gold-catalyzed Nazarov cyclization to rapidly construct the 6-5-5-5 tetracyclic skeleton.
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December 2024
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
E-cigarette/vaping-associated lung injury (EVALI) is strongly associated with vitamin E acetate and often occurs with concomitant tetrahydrocannabinol (THC) use. To uncover pathways associated with EVALI, we examined cytokines, transcriptomic signatures, and lipidomic profiles in bronchoalveolar lavage fluid (BALF) from THC-EVALI patients. At a single center, we prospectively enrolled mechanically ventilated patients with EVALI from THC-containing products (N = 4) and patients with non-vaping acute lung injury and airway controls (N = 5).
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December 2024
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
Lipid nanoparticles (LNPs) have proven effective in mRNA delivery, as evidenced by COVID-19 vaccines. Its key ingredient, ionizable lipids, is traditionally optimized by inefficient and costly experimental screening. This study leverages artificial intelligence (AI) and virtual screening to facilitate the rational design of ionizable lipids by predicting two key properties of LNPs, apparent pKa and mRNA delivery efficiency.
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