Alternative splicing plays a key role in posttranscriptional regulation of gene expression, allowing a single gene to encode multiple protein isoforms. As such, alternative splicing amplifies the coding capacity of the genome enormously, generates protein diversity, and alters protein function. More than 90% of human genes undergo alternative splicing, and alternative splicing is especially prevalent in the nervous and immune systems, tissues where cells need to react swiftly and adapt to changes in the environment through carefully regulated mechanisms of cell differentiation, migration, targeting, and activation. Given its prevalence and complexity, this highly regulated mode of gene expression is prone to be affected by disease. In the following review, we look at how alternative splicing of signaling molecules—cytokines and their receptors—changes in different pathological conditions, from chronic inflammation to neurologic disorders, providing means of functional interaction between the immune and neuroendocrine systems. Switches in alternative splicing patterns can be very dynamic and can produce signaling molecules with distinct or antagonistic functions and localization to different subcellular compartments. This newly discovered link expands our understanding of the biology of immune and neuroendocrine cells, and has the potential to open new windows of opportunity for treatment of neurodegenerative disorders.

The poultry farming industry encounters considerable obstacles stemming from viral diseases, resulting in elevated mortality rates and substantial economic losses. Current research highlights the significant involvement of long non-coding RNAs (lncRNAs) in the interactions between hosts and pathogens by enhancing antiviral responses at different levels, such as the activation of pathogen recognition receptors, as well as through epigenetic, transcriptional, and post-transcriptional modifications. Specific long non-coding RNAs (lncRNAs), including ERL lncRNA, linc-GALMD3, and loc107051710, have been recognized as significant contributors to the antiviral immune response to multiple avian viral pathogens. Understanding the mechanisms by which long non-coding RNAs (lncRNAs) act offers valuable insights into prospective diagnostic and therapeutic approaches aimed at improving disease resistance in poultry. Differentially expressed lncRNAs may also be utilized as biomarkers for both prognosis and diagnosis of avian viral diseases. This review delves into the various roles of long non-coding RNAs (lncRNAs) in the context of viral diseases in chickens, such as avian leukosis, Marek’s disease, infectious bursal disease, avian influenza, infectious bronchitis, and Newcastle disease. It highlights the pivotal role of lncRNAs in the complex dynamics between the host and viral pathogens, particularly their interactions with specific viral proteins. Understanding these interactions may provide valuable insights into the spatial and temporal regulation of lncRNAs, aid in the identification of potential drug targets, and reveal the expression patterns of lncRNA and coding gene transcripts in response to different viral infections in avian species.

Nanobodies (single-domain antibodies, VHHs) have emerged as versatile tools for evaluating and treating Alzheimer’s disease (AD). They offer distinct engineering benefits compared with traditional antibodies and small molecules, including small size, stability, and specificity. In AD, nanobodies have been shown in preclinical models to neutralize toxic amyloid-β oligomers, inhibit tau generation and aggregation, and modulate neuroinflammation, thereby demonstrating significant therapeutic potential. However, all nanobody applications in AD are discussed strictly as preclinical therapeutic potential rather than established clinical therapies, and direct clinical evidence in patients with AD is still lacking. Advanced engineering strategies, including intranasal and intrathecal routes, receptor-mediated transport, plasma protein binding with albumin, and focused ultrasound to facilitate brain penetration. Additionally, to improve nanobody delivery precision, half-life, and efficacy, strategies such as integrating nanobodies with nanoparticles, dendrimers, liposomes, and viral vectors are being employed. In fact, nanobodies are applied beyond monotherapy across multiple technological platforms to optimize brain delivery and target multiple targets. Nanobodies have been used on bispecific and trispecific antibody platforms, as well as in CRISPR/Cas9 editing and AI-driven technologies, to expand their applications. Recently, preclinical evidence has been mounting on the efficacy of nanobodies in clearing Aβ and tau, preserving synapses, and normalizing biomarkers. Comparison with FDA-approved anti-Aβ monoclonal antibodies (aducanumab, lecanemab, and donanemab) highlights opportunities and current translational gaps, including safety testing, half-life extension, and delivery optimization. This review critically delineates the current molecular mechanisms, emerging strategies, and delivery platforms, and emphasizes the potential of nanobodies as promising therapeutic and diagnostic molecules in AD therapeutics.

Since its discovery in 2001, Human Metapneumovirus (hMPV) has been identified globally, exhibiting predictable seasonal outbreaks primarily affecting young children, the elderly, and individuals with preexisting health conditions. The virus is transmitted through airborne droplets and is responsible for a notable percentage of respiratory illnesses, particularly in children under five years of age, with hospitalization rates peaking in the first year of life. The complex immune response elicited by hMPV, characterized by a Th17-like profile and excessive mucus production, contributes to respiratory complications, emphasizing the need for effective management strategies. This review discusses various diagnostic methods, emphasizing the potential of combining serology with RT-PCR to enhance diagnostic accuracy during outbreaks. Furthermore, it addresses the therapeutic approaches, including the promise of recombinant interferons and ongoing research on the use of passive immunity through neutralizing antibodies. A comprehensive overview of hMPV, emphasizing the importance of continued research to improve diagnostic and therapeutic options for this significant respiratory pathogen, offers promising strategies for manipulating responses through targeted interventions.

Interferon-gamma (IFN-γ) is a critical cytokine that plays a pivotal role in immune system regulation. It is a key mediator of both cellular defense mechanisms and antitumor immunity. As the sole member of the type II interferon family, IFN-γ modulates immune responses by activating macrophages, enhancing natural killer cell function, and regulating gene expression across multiple cellular processes. Alternative splicing is a post-transcriptional gene expression regulatory mechanism that generates multiple mature messenger RNAs from a single gene, dramatically increasing proteome diversity without the need of a proportional genome expansion. This process occurs in 90–95% of human genes, with alternative splicing events allowing for the production of diverse protein isoforms that can have distinct—or even opposing—functional properties. Alternative splicing plays a crucial role in cancer immunology, potentially generating tumor neoepitopes and modulating immune responses. However, how alternative splicing affects IFN-γ’s activity is still poorly understood. This review explores how alternative splicing regulates the expression and function of both upstream regulators and downstream effectors of IFN-γ, revealing complex mechanisms of gene expression and immune response modulation. Key transcription factors and signaling molecules of the IFN-γ pathway are alternatively spliced, and alternative splicing can dramatically alter IFN-γ signaling, immune cell function, and response to environmental cues. Specific splice variants can enhance or inhibit IFN-γ-mediated immune responses, potentially influencing cancer immunotherapy, autoimmune conditions, and infectious disease outcomes. The emerging understanding of these splicing events offers promising therapeutic strategies for manipulating immune responses through targeted molecular interventions.

Nanobodies (single-domain antibodies, VHHs) have emerged as versatile tools for evaluating and treating Alzheimer’s disease (AD). They offer unique advantages over traditional antibodies and small molecules, including small size, stability, and specificity. In AD, nanobodies were used to neutralize toxic amyloid-β oligomers, inhibit tau generation and aggregation, and modulate neuroinflammation, thereby demonstrating significant therapeutic potential. The delivery of nanobodies requires advanced strategies, including intranasal and intrathecal routes, receptor-mediated transport, plasma protein binding with albumin, and focused ultrasound to facilitate brain penetration. Additionally, to improve nanobody delivery precision, half-life, and efficacy, strategies such as integrating nanobodies with nanoparticles, dendrimers, liposomes, and viral vectors are being employed. In fact, nanobodies are applied beyond monotherapy across multiple technological platforms to optimize brain delivery and target multiple targets. Nanobodies have been used on bispecific and trispecific antibody platforms, as well as in CRISPR/Cas9 editing and AI-driven technologies, to expand their applications. Recently, preclinical evidence has been mounting on the efficacy of nanobodies in clearing Aβ and tau, preserving synapses, and normalizing biomarkers. Notably, clinical trials of bispecific antibodies, including trontinemab, are signaling translational progress and regulatory approvals, and further support would validate this class of therapeutic molecules. This review critically delineates the current molecular mechanisms, emerging strategies, and delivery platforms, and emphasizes the potential of nanobodies as promising therapeutic and diagnostic molecules in AD therapeutics.