Evolution of Alzheimer’s Disease Therapeutics: From Conventional Drugs to Medicinal Plants, Immunotherapy, Microbiotherapy and Nanotherapy

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(1), P. 128 - 128

Published: Jan. 17, 2025

Alzheimer's disease (AD) represents an escalating global health crisis, constituting the leading cause of dementia among elderly and profoundly impairing their quality life. Current FDA-approved drugs, such as rivastigmine, donepezil, galantamine, memantine, offer only modest symptomatic relief are frequently associated with significant adverse effects. Faced this challenge in line advances understanding pathophysiology neurodegenerative condition, various innovative therapeutic strategies have been explored. Here, we review novel approaches inspired by advanced knowledge underlying pathophysiological mechanisms disease. Among alternatives, immunotherapy stands out, employing monoclonal antibodies to specifically target eliminate toxic proteins implicated AD. Additionally, use medicinal plants is examined, synergistic effects components may confer neuroprotective properties. The modulation gut microbiota also addressed a peripheral strategy that could influence neuroinflammatory degenerative processes brain. Furthermore, potential emerging approaches, microRNAs regulate key cellular nanotherapy, which enables precise drug delivery central nervous system, analyzed. Despite promising these strategies, incidence continues rise. Therefore, it proposed achieving effective treatment future require integration combined maximizing different interventions.

Language: Английский

---

Pre-treated Mesenchymal Stem Cell-Derived Exosomes: A New Perspective for Accelerating Spinal Cord Injury Repair

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 992, P. 177349 - 177349

Published: Feb. 5, 2025

Spinal cord injury (SCI) is a devastating event for the central nervous system (CNS), often resulting in loss of sensory and motor functions. It profoundly affects both physiological psychological well-being patients, reducing their quality life while also imposing significant economic pressure on families healthcare system. Due to complex pathophysiology SCI, effective treatments promoting recovery remain scarce. Mesenchymal stem cell-derived exosomes (MSC-Exos) offer advantages such as low immunogenicity, good biocompatibility, ability cross blood-spinal barrier (BSCB). In preclinical studies, they have progressively shown efficacy SCI repair functional recovery. However, yield insufficient targeting MSC-Exos limit therapeutic efficacy. Currently, genetic engineering other preprocessing techniques are being employed optimize properties exosomes, thereby enhancing potential. Therefore, this paper provides an overview biogenesis exosomes. summarizes current approaches optimizing exosome performance. Additionally, it details mechanisms through which optimized provide neuroprotection explores potential combined involving hydrogels.

Language: Английский

---

Therapeutic Potential of TPT-260 in Ischemic Stroke: An Investigation Into Its Anti-Inflammatory Effects and Impact on Microglial Activation

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 3055 - 3066

Published: March 1, 2025

Ischemic stroke is characterized by a high incidence and elevated mortality. events trigger neuroinflammation, leading to severe brain edema neuronal necrosis. Microglia are the primary mediators of neuroinflammation. Inhibition M1 microglia effectively alleviate damage in mild stroke. TPT-260 minimally cytotoxic, small molecule chaperone retromer complex, which mediates recycling trafficking membrane protein receptors. This study explores therapeutic effects related mechanisms model mice from an anti-inflammatory perspective, aiming evaluate efficacy mechanism treating In this study, middle cerebral artery occlusion (MCAO) animal was established simulate ischemic Primary were cultured for lipopolysaccharides treatment construct microglia. Both animals cells treated with TPT-260. Nuclear factor-κB (NF-κB) nuclear translocation expression downstream pro-inflammatory factors Interleukin 1β (IL-1β) Tumor necrosis factor-α (TNF-α) determined. vivo results revealed that significantly reduced infarct area inflammation as well improved neurological function mice. The potential involved marked inhibition lipopolysaccharides-induced suppressing NF-κB attenuating IL-1β TNF-α. Moreover, inhibited NOD-like receptor 3 inflammasome formation, thereby decreasing release mature alleviating attenuated via repression signaling, thus preventing neuroinflammation injuries

Language: Английский

---

Challenges and opportunities for repairing the injured spinal cord: inflammation, regeneration, and functional reconstruction

Regenerative medicine reports ., Journal Year: 2025, Volume and Issue: 2(1), P. 36 - 44

Published: March 1, 2025

Spinal cord injury is a leading cause of disability worldwide, with profound physical, psychological, and socioeconomic impacts. Despite advances in medical care, there remains an urgent need for effective treatments that minimize side effects while promoting recovery. Prompt intervention following spinal crucial, as it has the potential to mitigate secondary damage improve outcomes. Among responses injury, neuroinflammation plays central role driving pathological progression both acute chronic phases injury. This complex physiological response, triggered by mechanical, chemical, or immunological insults, involves cascade cellular molecular events can either exacerbate tissue support repair recovery, depending on its regulation. In this review, we provide comprehensive overview primary inflammatory mechanisms arise detailing key players mediators involved. We also examine dual nature neuroinflammation, highlighting detrimental reparative roles context pathology. Furthermore, explore emerging therapeutic strategies aimed at modulating inflammation enhance functional Particular focus been placed recent preclinical studies using animal models evaluate novel anti-inflammatory agents. These findings underscore targeting promising avenue repair, paving way finding promote nerve regeneration

Language: Английский

---

Effect of Engineered Cyanobacterial Capsules on a Neurogenic Bladder after Spinal Cord Injury

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

The presence of a neurogenic bladder is severe but common complication spinal cord injury (SCI). Multiple pathological factors, such as hypoxia, ischemia, and oxidative stress caused by SCI, promote M1 microglial polarization the release proinflammatory factors to amplify inflammation. An excessive inflammatory response stimulates generation reactive oxygen species (ROS) induces neuronal ferroptosis, thus leading dysfunction after SCI. Therefore, promoting recovery neural function regulating interaction between microglia neurons important. For this purpose, we developed an engineered immunoregulatory cyanobacterial capsule named siRNA@Cyanzyme, which consists MnO2@zeolitic-imidazolate framework@cyanobacteria (Cyanzyme) small-interfering RNA targeting ACSL4 (siRNA-ACSL4). Cyanzyme reversed via photosynthetic anti-inflammatory factor release. MnO2 nanoenzymes grown on surface ZIF-8 eliminated ROS reduce stress. Moreover, increased delivery efficiency siRNA-ACSL4, key regulator ferroptosis. Both treatments alleviated GABAergic neuron damage mitigate dysfunction. Our data demonstrated that siRNA@Cyanzyme effectively polarization, reduced ultimately restored function.

Language: Английский

---

Plexin B2 in physiology and pathophysiology of the central nervous system

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 155, P. 114627 - 114627

Published: April 14, 2025

Language: Английский

---

Exosome-based therapy for spinal cord injury: a narrative review

Advanced technology in neuroscience ., Journal Year: 2025, Volume and Issue: unknown

Published: May 12, 2025

Currently, treatments such as stem cell transplantation, gene therapy, and anti-inflammatory approaches have shown some promise in addressing spinal cord injury. However, there is still a lack of more effective treatment options. Thus, improved strategies are needed to enhance efficacy promote functional recovery. Exosome-based therapy has emerged promising strategy because exosomes can deliver bioactive molecules, modulate inflammation, tissue regeneration. This review highlights recent advancements the use derived from various types, including mesenchymal cells macrophages, for Exosomes nanoscale vesicles secreted by that involved transporting biomolecules, regulating intercellular communication, reducing inflammatory responses, promoting angiogenesis, providing neuroprotection. The article discusses diagnostic, therapeutic, prognostic roles exosomes, along with administration methods. It mechanisms which different types facilitate injury repair, nerve regeneration, inhibiting apoptosis, an antioxidant stress response. Additionally, emerging techniques engineered targeted delivery systems explored therapeutic specificity. Although exosome faces challenges, need standardized preparation, precise delivery, dose optimization, bioengineered show potential. Overall, exosome-based technology neuroscience offers new perspectives methods treating injury, potential improve recovery patients, thereby warranting future clinical translation.

Language: Английский

---

Current multi-scale biomaterials for tissue regeneration following spinal cord injury

Neurochemistry International, Journal Year: 2024, Volume and Issue: 178, P. 105801 - 105801

Published: July 5, 2024

Language: Английский

---

The Role of Inflammatory Cascade and Reactive Astrogliosis in Glial Scar Formation Post-spinal Cord Injury

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: Nov. 23, 2024

Reactive astrogliosis and inflammation are pathologic hallmarks of spinal cord injury. After injury, dysfunction glial cells (astrocytes) results in scar formation, which limits neuronal regeneration. The blood–spinal barrier maintains the structural functional integrity does not allow blood vessel components to leak into microenvironment. disruption causes an imbalance immunological This triggers process neuroinflammation, facilitated by actions microglia, neutrophils, cells, cytokines production. Recent work has revealed two phenotypes astrocytes, A1 A2, where A2 a protective type, releases neurotoxins, further promoting formation. Here, we first describe current understanding microenvironment, both pre-, post-injury, role different context forms essential update on cellular molecular events following We aim explore in-depth signaling pathways mediators that trigger astrocyte activation review will discuss activated astrocytes other their collaborative development gliosis through inflammatory responses.

Language: Английский

---

Microglia-specific transduction via AAV11 armed with IBA1 promoter and miRNA-9 targeting sequences

Published: July 13, 2024

Abstract Microglia, as resident immune cells in the central nervous system (CNS), are closely related to human health and pathogenesis of various CNS diseases, making them compelling targets for therapeutic interventions. However, functional studies microglia remain significant challenges largely due lack tools capable efficiently specifically transducing microglia. Herein, we evaluated specificity efficiency adeno-associated virus (AAV) vectors armed with mIBA1 promoter miRNA-9 targeting sequences within caudate putamen (CPu) brain region, found that AAV11 mediates more specific efficient transduction Subsequently, further demonstrated also exhibits high across areas spinal cord. Finally, by reducing injection dosage, employed sparse labeling This work provides a promising tool advancing both investigation

Language: Английский

---