Research progress on exosome-mediated vascular endothelial growth factor–nerve growth factor cotransplantation in the treatment of Parkinson’s disease

Deleted Journal, Journal Year: 2025, Volume and Issue: 2(1), P. 11 - 15

Published: Jan. 13, 2025

The significant decrease in dopamine (DA) neurotransmitter levels the brain due to degeneration and loss of dopaminergic neurons is one main reasons for causes motor symptoms Parkinson disease. Vascular endothelial growth factor has been proven have a protective effect on DA neurons. Its synergistic interaction with nerve can accelerate repair damaged nerves improve central nervous system. However, presence blood-brain barrier hinders most drugs from entering brain. Exosomes are class nanoscale extracellular vesicles advantages such as higher safety, low immunogenicity, unique targeted homing ability, efficient penetration barrier, which open new perspective drug delivery system provide possibilities treatment neurodegenerative diseases. This article reviews research progress exosomes above 2 factors repair, ideas

Language: Английский

---

Blood-Based Biomarkers in Alzheimer’s Disease: Advancing Non-Invasive Diagnostics and Prognostics

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 10911 - 10911

Published: Oct. 10, 2024

Alzheimer’s disease (AD), the most prevalent form of dementia, is expected to rise dramatically in incidence due global population aging. Traditional diagnostic approaches, such as cerebrospinal fluid analysis and positron emission tomography, are expensive invasive, limiting their routine clinical use. Recent advances blood-based biomarkers, including amyloid-beta, phosphorylated tau, neurofilament light, offer promising non-invasive alternatives for early AD detection monitoring. This review synthesizes current research on these highlighting potential track pathology enhance accuracy. Furthermore, this uniquely integrates recent findings protein-protein interaction networks microRNA pathways, exploring novel combinations proteomic, genomic, epigenomic biomarkers that provide new insights into AD’s molecular mechanisms. Additionally, we discuss integration with advanced neuroimaging techniques, emphasizing revolutionize diagnostics. Although large-scale validation still needed, represent a critical advancement toward more accessible, cost-effective, tools AD.

Language: Английский

---

Beyond vessels: unraveling the impact of VEGFs on neuronal functions and structure

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: March 6, 2025

Neurons rely on the bloodstream for essential nutrients and oxygen, which is facilitated by an intricate coupling of neuronal vascular systems. Central to this neurovascular interaction endothelial growth factor (VEGF) family, a group secreted factors traditionally known their roles in promoting cell proliferation, migration, survival cardiovascular lymphatic However, emerging evidence shows that VEGFs also play indispensable nervous system, extending beyond canonical angiogenic lymphangiogenic functions. Over past two decades, have been found exert direct effects neurons, influencing key aspects function independently actions cells. In particular, it has become increasingly evident crucial functions development, regulation, maintenance morphology. Understanding development high scientific clinical interest because significance precise morphology neural connectivity network function, as well association morphological abnormalities with neurological neurodegenerative disorders. This review begins overview VEGF family members, structural characteristics, receptors, established vasculature. then highlights focuses exciting variety VEGFs, especially role

Language: Английский

---

Exercise, Neuroprotective Exerkines, and Parkinson’s Disease: A Narrative Review

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1241 - 1241

Published: Sept. 30, 2024

Parkinson's disease (PD) is a prevalent neurodegenerative in which treatment often includes an exercise regimen. Exercise neuroprotective animal models of PD, and, more recently, human clinical studies have verified exercise's disease-modifying effect. Aerobic and resistance training improve many PD's motor non-motor symptoms, while neuromotor therapy stretching/flexibility exercises positively contribute to the quality life people with PD. Therefore, understanding role managing this complex disorder crucial. Exerkines are bioactive substances that synthesized released during been implicated several positive health outcomes, including neuroprotection. protect neuronal cells vitro rodent PD vivo. both increase exerkine levels blood, suggesting for exerkines theory. Many demonstrate potential protecting brain against pathological missteps caused by Every person (people) (PwP) needs comprehensive plan tailored their unique abilities. Here, we provide template help PwP understand importance treating describe barriers confronting attempt exercise, suggestions overcoming these barriers, explore In conclusion, together create powerful system should slowing chronic progression

Language: Английский

---

Microglia Morphological Response to Mesenchymal Stromal Cell Extracellular Vesicles Demonstrates EV Therapeutic Potential for Modulating Neuroinflammation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 3, 2024

ABSTRACT Background Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) are a promising therapeutic for neuroinflammation. MSC-EVs can interact with microglia, the resident immune cells of brain, to exert their immunomodulatory effects. In response inflammatory cues, such as cytokines, microglia undergo phenotypic changes indicative function e.g. morphology and secretion. However, these in not well understood. Additionally, no disease-relevant screening tools assess MSC-EV bioactivity exist, which has further impeded clinical translation. Here, we developed quantitative, high throughput morphological profiling approach neuroinflammation-relevant signals whether this be used indicate MSC-EVs. Results Using an immortalized human cell-line, observed increased size (perimeter, major axis length) complexity (form factor) upon stimulation interferon-gamma (IFN-γ) tumor necrosis factor-alpha (TNF-α). Upon treatment MSC-EVs, overall score (determined using principal component analysis) shifted towards unstimulated morphology, indicating that bioactive modulate microglia. The effects TNF-γ/IFN-α stimulated were concomitant reduced secretion 14 chemokines/cytokines (e.g. CXCL6, CXCL9) 12 CXCL8, CXCL10). Proteomic analysis lysates revealed significant increases 192 proteins HIBADH, MEAK7, LAMC1) decreases 257 PTEN, TOM1, MFF) treatment. Of note, many involved regulation migration. Gene Set Variation Analysis upregulation pathways associated response, cytokine production, infiltration T cells, NK cells) Semaphorin, RHO/Rac signaling). mitochondrial measured suggesting metabolism. Conclusion This study comprehensively demonstrates on microglial secretion, cellular proteome, content. Our high-throughput, rapid, low-cost enables batches manufacturing conditions enhance EV mitigate functional heterogeneity disease relevant manner. is highly generalizable adapted refined based selection signal, target cell, product.

Language: Английский

---

New BDNF and NT-3 Cyclic Mimetics Concur with Copper to Activate Trophic Signaling Pathways as Potential Molecular Entities to Protect Old Brains from Neurodegeneration

Biomolecules, Journal Year: 2024, Volume and Issue: 14(9), P. 1104 - 1104

Published: Sept. 2, 2024

A low level of Neurotrophins (NTs), their Tyrosine Kinase Receptors (Trks), Vascular Endothelial Growth Factors (VEGFs) and receptors, mainly VEGFR1 VEGFR2, characterizes AD brains. The use NTs VEGFs as drugs presents different issues due to permeability the blood−brain barrier, poor pharmacokinetic profile, relevant side effects. To overcome these issues, functional structural NT mimics have been employed. Being aware that N-terminus domain key for binding selectivity activation Trks need avoid or delay proteolysis, we herein report on mimicking ability two cyclic peptide encompassing Brain Derived Factor (BDNF), (c-[HSDPARRGELSV-]), cBDNF(1-12) Neurotrophin3 (NT3), (c-[YAEHKSHRGEYSV-]), cNT3(1-13). features were characterized by a combined thermodynamic spectroscopic approach (potentiometry, NMR, UV-vis CD) was extended copper(II) ion complexes. SH-SY5Y cell assays show Cu2+ present at sub-micromolar in complete culture media affects treatments with peptides. cNT3(1-13) act ionophores, induce neuronal differentiation promote CREB phosphorylation copper dependent manner. Consistently, both stimulate BDNF VEGF expression well release; VEGFRs.

Language: Английский

---

Microglia morphological response to mesenchymal stromal cell extracellular vesicles demonstrates EV therapeutic potential for modulating neuroinflammation

Journal of Biological Engineering, Journal Year: 2024, Volume and Issue: 18(1)

Published: Oct. 17, 2024

Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) are a promising therapeutic for neuroinflammation. MSC-EVs can interact with microglia, the resident immune cells of brain, to exert their immunomodulatory effects. In response inflammatory cues, such as cytokines, microglia undergo phenotypic changes indicative function e.g. morphology and secretion. However, these in not well understood. Additionally, no disease-relevant screening tools assess MSC-EV bioactivity exist, which has further impeded clinical translation. Here, we developed quantitative, high throughput morphological profiling approach neuroinflammation- relevant signals whether this be used indicate MSC-EVs.

Language: Английский

---