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Dysregulation of Metabolic Peptides Precedes Hyperinsulinemia and Inflammation Following Exposure to Rotenone in Rats.
Cells
January 2025
Ralph H. Johnson Veterans Administration Medical Center, 109 Bee Street, Charleston, SC 29401, USA.
Rotenone, a naturally occurring compound derived from the roots of tropical plants, is used as a broad-spectrum insecticide, piscicide, and pesticide. It is a classical, high-affinity mitochondrial complex I inhibitor that causes not only oxidative stress, α-synuclein phosphorylation, DJ-1 (Parkinson's disease protein 7) modifications, and inhibition of the ubiquitin-proteasome system but it is also widely considered an environmental contributor to Parkinson's disease (PD). While prodromal symptoms, such as loss of smell, constipation, sleep disorder, anxiety/depression, and the loss of dopaminergic neurons in the substantia nigra of rotenone-treated animals, have been reported, alterations of metabolic hormones and hyperinsulinemia remain largely unknown and need to be investigated.
View Article and Find Full Text PDFBiological memory networks are thought to store information by experience-dependent changes in the synaptic connectivity between assemblies of neurons. Recent models suggest that these assemblies contain both excitatory and inhibitory neurons (E/I assemblies), resulting in co-tuning and precise balance of excitation and inhibition. To understand computational consequences of E/I assemblies under biologically realistic constraints we built a spiking network model based on experimental data from telencephalic area Dp of adult zebrafish, a precisely balanced recurrent network homologous to piriform cortex.
View Article and Find Full Text PDFRevolutionizing Parkinson's treatment: Harnessing the potential of intranasal nanoemulsions for targeted therapy.
Drug Deliv Transl Res
January 2025
Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, 136119, Haryana, India.
Parkinson's disease (PD) is the most prominent and highly prevalent chronic neuro-degenerative disease generally recognized by classical motor symptoms which are linked with genetic mutation, Lewy bodies, and subsequently selective loss of nigrostriatal dopaminergic neurons. The blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier protect the central nervous system against toxins and are the most significant barriers to effective brain drug delivery in managing Parkinsonism. In recent years, intranasal delivery has attracted remarkable attention for brain targeting as the drug can be administered to the brain directly from the nose employing the trigeminal and olfactory pathways.
View Article and Find Full Text PDFN-terminus α-synuclein detection reveals new and more diverse aggregate morphologies in multiple system atrophy and Parkinson's disease.
Transl Neurodegener
December 2024
Department of Anatomy and Medical Imaging, University of Auckland, 85 Park Road, Grafton, , Auckland, 1142, New Zealand.
Background: Parkinson's disease (PD) and multiple system atrophy (MSA) are classified as α-synucleinopathies and are primarily differentiated by their clinical phenotypes. Delineating these diseases based on their specific α-synuclein (α-Syn) proteoform pathologies is crucial for accurate antemortem biomarker diagnosis. Newly identified α-Syn pathologies in PD raise questions about whether MSA exhibits a similar diversity.
View Article and Find Full Text PDFTherapeutic effect of cyclosporine A-loading TPGS micelles on a mouse model of LPS-induced neuroinflammation.
Eur J Pharm Sci
February 2025
Laboratory of Pharmacology, Department of Pharmacy, University of Coimbra, Coimbra, Portugal; CIBIT/ICNAS - Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal. Electronic address:
Neuroinflammation is an undoubted hallmark of neurodegenerative processes characterized by memory impairment, loss of coordination and muscle strength in diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis as well as depressive disorders. Cyclosporine A (CSA) has already been identified as a promising neuroprotective peptide, due to its well-known anti-inflammatory properties. Herein, CSA was encapsulated into α-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles and intranasally administered to a lipopolysaccharide (LPS) induced mouse model of neuroinflammation.
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