Exploring the Potential of Aptamers in Targeting Neuroinflammation and Neurodegenerative Disorders: Opportunities and Challenges.

Neuroinflammation is the precursor for several neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Targeting neuroinflammation has emerged as a promising strategy to address a wide range of CNS pathologies. These NDDs still present significant challenges in terms of limited and ineffective diagnosis and treatment options, driving the need to explore innovative and novel therapeutic alternatives. Aptamers are single-stranded nucleic acids that offer the potential for addressing these challenges through diagnostic and therapeutic applications. In this review, we summarize diagnostic and therapeutic aptamers for inflammatory biomolecules, as well as the inflammatory cells in NDDs. We also discussed the potential of short nucleotides for Aptamer-Based Targeted Brain Delivery through their unique features and modifications, as well as their ability to penetrate the blood-brain barrier. Moreover, the unprecedented opportunities and substantial challenges of using aptamers as therapeutic agents, such as drug efficacy, safety considerations, and pharmacokinetics, are also discussed. Taken together, this review assesses the potential of aptamers as a pioneering approach for target delivery to the CNS and the treatment of neuroinflammation and NDDs.

Targeting calcium signaling by inositol trisphosphate receptors: A novel mechanism for the anti-asthmatic effects of Houttuynia cordata.

Asthma is a chronic inflammatory disease characterized by airway hypersensitivity and remodeling. The current treatments provide only short-term benefits and may have undesirable side effects; thus, alternative or supplementary therapy is needed. Because intracellular calcium (Ca2+) signaling plays an essential role in regulating the contractility and remodeling of airway smooth muscle cells, the targeting of Ca2+ signaling is a potential therapeutic strategy for asthma. Houttuynia cordata is a traditional Chinese herb that is used to treat asthma due to its anti-allergic and anti-inflammatory properties. We hypothesized that H. cordata might modulate intracellular Ca2+ signaling and could help relieve asthmatic airway remodeling. We found that the mRNA and protein levels of inositol trisphosphate receptors (IP3Rs) were elevated in interleukin-stimulated primary human bronchial smooth muscle cells and a house dust mite-sensitized model of asthma. The upregulation of IP3R expression enhanced intracellular Ca2+ release upon stimulation and contributed to airway remodeling in asthma. Intriguingly, pretreatment with H. cordata essential oil rectified the disruption of Ca2+ signaling, mitigated asthma development, and prevented airway narrowing. Furthermore, our analysis suggested that houttuynin/2-undecanone could be the bioactive component in H. cordata essential oil because we found similar IP3R suppression in response to the commercially available derivative sodium houttuyfonate. An in silico analysis showed that houttuynin, which downregulates IP3R expression, binds to the IP3 binding domain of IP3R and may mediate a direct inhibitory effect. In summary, our findings suggest that H. cordata is a potential alternative treatment choice that may reduce asthma severity by targeting the dysregulation of Ca2+ signaling.