Protecting dopaminergic neurons is a key approach in the prevention of Parkinson's disease (PD). Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel that is widely distributed in the mammalian nervous system. In this study, we designed experiments to investigate the effect and mechanisms of TRPV1 against DA neurons damage of PD. Our results showed that trpv1-deficient mice showed a significant loss of TH + neurons than PD mice after MPTP intraperitoneal injection, in addition, a significant decline in motor function was observed in trpv1-deficient mice versus the MPTP model. In addition, our study indicated that GDF11 overexpression inhibited MPP + - induced oxidative stress, cell senescence, and apoptosis in neurons. Results also showed that TRPV1 prevented the down-regulation of GDF11 expression in PD model, gdf11 knockdown blocks the effects of TRPV1 on the antioxidant, antiaging, and antiapoptotic activities of dopaminergic neurons. Consequently, our findings indicate that TRPV1 protects dopaminergic neurons from injury by promoting GDF11 expression in PD model.
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http://dx.doi.org/10.1016/j.bbrc.2022.07.058 | DOI Listing |
Adv Drug Deliv Rev
January 2025
Neurodegenerative Diseases Department, Kadimastem Ltd, Pinchas Sapir 7, Weizmann Science Park, Ness-Ziona, Israel; Department of Molecular Genetics, Weizmann Institute of Science, 76100, Rehovot, Israel.
Self-renewal capacity and potential to differentiate into almost any cell type of the human body makes pluripotent stem cells a valuable starting material for manufacturing of clinical grade cell therapies. Neurodegenerative diseases are characterized by gradual loss of structure or function of neurons, often leading to neuronal death. This results in gradual decline of cognitive, motor, and physiological functions due to the degeneration of the central nervous systems.
View Article and Find Full Text PDFBiomater Adv
January 2025
Department of Biomedical Sciences, National Chung Cheng University, Chia-Yi 62102, Taiwan, ROC.
Encapsulated BV6 and SM164, two bivalent second mitochondria-derived activator of caspase (Smac) mimetics, in etoposide (ETO)-lipopolymer nanoparticles (NPs) have been developed to deplete inhibitor of apoptosis proteins (IAP), impair DNA, and produce antagonistic effects on glioblastoma multiforme (GBM) in nude mice. The NPs, composed of cocoa butter (CB) and polyvinyl alcohol (PVA), were stabilized by glycerol monostearate and Pluronic F-127, and grafted with transferrin (Tf) and wheat germ agglutinin (WGA) to dock the blood-brain barrier (BBB) and degenerated dopaminergic neurons. The dual-targeting NPs increased the BBB permeability of BV6, SM164 and ETO via recognizing Tf receptor (TfR) and N-acetylglucosamine that are abundantly expressed on brain microvascular endothelial cells.
View Article and Find Full Text PDFBMC Neurosci
January 2025
Department of Operative Dentistry and Periodontology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein aggregates mostly consisting of misfolded alpha-synuclein (αSyn). Progressive degeneration of midbrain dopaminergic neurons (mDANs) and nigrostriatal projections results in severe motor symptoms. While the preferential loss of mDANs has not been fully understood yet, the cell type-specific vulnerability has been linked to a unique intracellular milieu, influenced by dopamine metabolism, high demand for mitochondrial activity, and increased level of oxidative stress (OS).
View Article and Find Full Text PDFMol Psychiatry
January 2025
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Age-related dopamine (DA) neuron loss is a primary feature of Parkinson's disease. However, whether similar biological processes occur during healthy aging, but to a lesser degree, remains unclear. We therefore determined whether midbrain DA neurons degenerate during aging in mice and humans.
View Article and Find Full Text PDFJ Neurochem
January 2025
Institute for Physiology, University of Tübingen, Tübingen, Germany.
Parkinson's disease (PD) is a prevalent neurodegenerative disease caused by the death of dopaminergic neurons within the substantia nigra pars compacta (SNpc) region of the midbrain. Recent genomic and single cell sequencing data identified oligodendrocytes and oligodendrocyte precursor cells (OPCs) to confer genetic risk in PD, but their biological role is unknown. Although SNpc dopaminergic neurons are scarcely or thinly myelinated, there is a gap in the knowledge concerning the physiological interactions between dopaminergic neurons and oligodendroglia.
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