Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 46(1), P. 45 - 61
Published: Dec. 17, 2024
Language: Английский
Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(2), P. 587 - 597
Published: Jan. 31, 2024
JOURNAL/nrgr/04.03/01300535-202502000-00034/figure1/v/2024-05-28T214302Z/r/image-tiff Several studies have found that transplantation of neural progenitor cells (NPCs) promotes the survival injured neurons. However, a poor integration rate and high risk tumorigenicity after cell limits their clinical application. Small extracellular vesicles (sEVs) contain bioactive molecules for neuronal protection regeneration. Previous shown stem/progenitor cell-derived sEVs can promote recovery neurological function in neurodegenerative eye diseases other diseases. In this study, we intravitreally transplanted derived from human induced pluripotent stem (hiPSCs) hiPSCs-differentiated NPCs (hiPSC-NPC) mouse model optic nerve crush. Our results show these injected were ingested by retinal cells, especially those localized ganglion layer. Treatment with hiPSC-NPC-derived mitigated crush-induced degeneration, regulated microenvironment inhibiting excessive activation microglia. Component analysis further revealed hiPSC-NPC transported neuroprotective anti-inflammatory miRNA cargos to target which had protective effects on RGCs injury. These findings suggest are promising cell-free therapeutic strategy neuropathy.
Language: Английский
Citations
5
Science Advances, Journal Year: 2024, Volume and Issue: 10(31)
Published: Aug. 2, 2024
As part of the central nervous system, optic nerve, composed axons from retinal ganglion cells (RGCs), generally fails to regenerate on its own when injured in adult mammals. An innovative approach promoting nerve regeneration involves manipulating interactions between amacrine (ACs) and RGCs. Here, we identified a unique AC subtype, dopaminergic ACs (DACs), that responded early after crush by down-regulating neuronal activity reducing dopamine (DA) release. Activating DACs or augmenting DA release with levodopa demonstrated neuroprotective effects modestly enhanced axon regeneration. Within this context, pinpointed receptor D1 (DRD1) as critical mediator DAC-derived showed RGC-specific Drd1 overexpression effectively overcame subtype-specific barriers This strategy markedly boosted RGC survival preserved vision glaucoma model. study unveils crucial role signaling regeneration, holding promise for therapeutic insights into neural repair.
Language: Английский
Citations
4
Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 9, 2025
Retinal ganglion cells (RGCs) generally fail to regenerate axons, resulting in irreversible vision loss after optic nerve injury. While many studies have shown that modulating specific genes can enhance RGCs survival and promote regeneration, inducing long-distance axon regeneration vivo through single-gene manipulation remains challenging. Nevertheless, combined multi-gene therapies proven effective significantly enhancing axonal regeneration. At present, research on promoting slow, with most unable achieve growth beyond the chiasm or reestablish connections brain. Future priorities include directing along correct pathways, facilitating synapse formation myelination, modifying inhibitory microenvironment. These strategies are crucial not only for but also broader applications central nervous system repair. In this review, we discuss multifactors therapeutic offering insights into advancing research.
Language: Английский
Citations
0
Materials Today Bio, Journal Year: 2025, Volume and Issue: unknown, P. 101670 - 101670
Published: March 1, 2025
Development of novel therapeutics for retinal ganglion cells (RGCs) protection and axon regeneration in neurodegenerative diseases, example, glaucoma, are critical challenges clinical treatment. Utilization N, N', N'-tetrakis-(2-Pyridylmethyl) ethylenediamine (TPEN), a specific chelator Zn2+, revealed positive medical potentials. However, its therapeutic effect promoting RGCs survival is restricted due to the inefficient drug delivery limited absorption. To address this, this work developed nanoparticles (NPs)-based system with sustained release TPEN, using oil-in-water (O/W) single-emulsion solvent evaporation method various surfaces coatings. Optic nerve crush (ONC) acute ocular hypertension (AOH) animal models were carried out investigate neuroprotective regenerative effects TPEN-loaded NPs. was systematically assessed through whole-mount retina immunostaining hematoxylin eosin staining histological changes. Electroretinography used evaluating visual function Axon evaluated by SMI32 stain intravitreal administration cholera Toxin Subunit B (CTB), respectively. In vivo, NPs achieved comparable on neuroprotection after ONC, reduced frequency vitreous injection half TPEN dosage compared solution. meantime, also more effectively preserved Additionally, AOH significantly enhanced treating The show promise pre-clinical testing neuro-regenerative therapies glaucoma other diseases.
Language: Английский
Citations
0
ACS Nano, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 23, 2024
Macrophages are rapidly activated and polarized toward the M1 phenotype after spinal cord injury (SCI), inhibiting M1-like macrophages has emerged as a promising SCI treatment approach. Metalloregulatory proteins, which sense specific metal ions with high affinity specificity, play critical role in immune regulation. Here, we screened various bioactive associated metalloregulatory proteins discovered that Zn2+ Mn2+ effectively suppressed polarization. Based on these findings, mildly alkaline ZnMn-based layered double hydroxides (ZnMn-LDHs) self-assembled from coordinated were developed to inhibit macrophages. ZnMn-LDHs neutralized acidic environment promoted expression of including metallothionein (MT), superoxide dismutase 1 (SOD1), 2 (SOD2), thereby eliciting robust macrophage inhibition. More importantly, nerve growth factor (NGF) released by following regulation elongation spreading Schwann cells. By integrating silk fibroin (SF), ZnMn@SF injectable hydrogels constructed for repair. An vivo animal model further revealed excellent anti-inflammatory effects treating SCI, functional recovery. Our findings underscore importance regulated macrophages, providing therapeutic strategy treatment.
Language: Английский
Citations
2
Neuropharmacology, Journal Year: 2023, Volume and Issue: 242, P. 109746 - 109746
Published: Oct. 12, 2023
Language: Английский
Citations
5
AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 326(5), P. C1293 - C1307
Published: March 25, 2024
Our study explores zinc’s pivotal role in mitigating extracellular matrix dysregulation the trabecular meshwork and glucocorticoid-induced ocular hypertension. We found that human cells treated with dexamethasone, intracellular Zn 2+ significantly decreased, accompanied by impaired uptake. Zinc supplementation rescues visual function modulating proteins lowering intraocular pressure, offering a direction for further exploration glaucoma management.
Language: Английский
Citations
1
Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 212, P. 415 - 432
Published: Dec. 20, 2023
Language: Английский
Citations
3
Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 46(1), P. 45 - 61
Published: Dec. 17, 2024
Language: Английский
Citations
0