An overview of early genetic predictors of IgA deficiency.

INTRODUCTION: Inborn errors of immunity (IEIs) refer to a heterogeneous category of diseases with defects in the number and/or function of components of the immune system. Immunoglobulin A (IgA) deficiency is the most prevalent IEI characterized by low serum level of IgA and normal serum levels of IgG and/or IgM. Most of the individuals with IgA deficiency are asymptomatic and are only identified through routine laboratory tests. Others may experience a wide range of clinical features including mucosal infections, allergies, and malignancies as the most important features. IgA deficiency is a multi-complex disease, and the exact pathogenesis of it is still unknown. AREAS COVERED: This review compiles recent research on genetic and epigenetic factors that may contribute to the development of IgA deficiency. These factors include defects in B-cell development, IgA class switch recombination, synthesis, secretion, and the long-term survival of IgA switched memory B cells and plasma cells. EXPERT OPINION: A better and more comprehensive understanding of the cellular pathways involved in IgA deficiency could lead to personalized surveillance and potentially curative strategies for affected patients, especially those with severe symptoms.

Stem cell therapies for neurological disorders: current progress, challenges, and future perspectives.

Stem cell-based therapies have emerged as a promising approach for treating various neurological disorders by harnessing the regenerative potential of stem cells to restore damaged neural tissue and circuitry. This comprehensive review provides an in-depth analysis of the current state of stem cell applications in primary neurological conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and other related disorders. The review begins with a detailed introduction to stem cell biology, discussing the types, sources, and mechanisms of action of stem cells in neurological therapies. It then critically examines the preclinical evidence from animal models and early human trials investigating the safety, feasibility, and efficacy of different stem cell types, such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs). While ESCs have been studied extensively in preclinical models, clinical trials have primarily focused on adult stem cells such as MSCs and NSCs, as well as iPSCs and their derivatives. We critically assess the current state of research for each cell type, highlighting their potential applications and limitations in different neurological conditions. The review synthesizes key findings from recent, high-quality studies for each neurological condition, discussing cell manufacturing, delivery methods, and therapeutic outcomes. While the potential of stem cells to replace lost neurons and directly reconstruct neural circuits is highlighted, the review emphasizes the critical role of paracrine and immunomodulatory mechanisms in mediating the therapeutic effects of stem cells in most neurological disorders. The article also explores the challenges and limitations associated with translating stem cell therapies into clinical practice, including issues related to cell sourcing, scalability, safety, and regulatory considerations. Furthermore, it discusses future directions and opportunities for advancing stem cell-based treatments, such as gene editing, biomaterials, personalized iPSC-derived therapies, and novel delivery strategies. The review concludes by emphasizing the transformative potential of stem cell therapies in revolutionizing the treatment of neurological disorders while acknowledging the need for rigorous clinical trials, standardized protocols, and multidisciplinary collaboration to realize their full therapeutic promise.

Immune landscape of hepatocellular carcinoma: From dysregulation of the immune responses to the potential immunotherapies.

Hepatocellular carcinoma (HCC) presents a considerable global health burden due to its late diagnosis and high morbidity. The liver's specific anatomical and physiological features expose it to various antigens, requiring precise immune regulation. To the best of our knowledge, this is the first time that a comprehensive overview of the interactions between the immune system and gut microbiota in the development of HCC, as well as the relevant therapeutic approaches are discussed. Dysregulation of immune compartments within the liver microenvironment drives HCC pathogenesis, characterized by elevated regulatory cells such as regulatory T cells (Tregs), myeloid-derived suppressor cells, and M2 macrophages as well as suppressive molecules, alongside reduced number of effector cells like T cells, natural killer cells, and M1 macrophages. Dysbiosis of gut microbiota also contributes to HCC by disrupting intestinal barrier integrity and triggering overactivated immune responses. Immunotherapy approaches, particularly immune checkpoint inhibitors, have exhibited promise in HCC management, yet adoptive cell therapy and cancer vaccination research are in the early steps with relatively less favorable outcomes. Further understanding of immune dysregulation, gut microbiota involvement, and therapeutic combination strategies are essential for advancing precision immunotherapy in HCC.

Clinical, Immunological, and Genetic Features in Patients with NFKB1 and NFKB2 Mutations: a Systematic Review.

BACKGROUND: Inborn errors of immunity (IEIs) encompass various diseases with diverse clinical and immunological symptoms. Determining the genotype-phenotype of different variants in IEI entity precisely is challenging, as manifestations can be heterogeneous even in patients with the same mutated gene. OBJECTIVE: In the present study, we conducted a systematic review of patients recorded with NFKB1 and NFKB2 mutations, two of the most frequent monogenic IEIs. METHODS: The search for relevant literature was conducted in databases including Web of Science, PubMed, and Scopus. Information encompassing demographic, clinical, immunological, and genetic data was extracted from cases reported with mutations in NFKB1 and NFKB2. The comprehensive features of manifestations in patients were described, and a comparative analysis of primary characteristics was conducted between individuals with NFKB1 loss of function (LOF) and NFKB2 (p52-LOF/IκBδ-gain of function (GOF)) variants. RESULTS: A total of 397 patients were included in this study, 257 had NFKB1 mutations and 140 had NFKB2 mutations. There were 175 LOF cases in NFKB1 and 122 p52LOF/IκBδGOF cases in NFKB2 pivotal groups with confirmed functional implications. NFKB1LOF and p52LOF/IκBδGOF predominant cases (81.8% and 62.5% respectively) initially presented with a CVID-like phenotype. Patients with NFKB1LOF variants often experienced hematologic autoimmune disorders, whereas p52LOF/IκBδGOF patients were more susceptible to other autoimmune diseases. Viral infections were markedly higher in p52LOF/IκBδGOF cases compared to NFKB1LOF (P-value < 0.001). NFKB2 (p52LOF/IκBδGOF) patients exhibited a greater prevalence of ectodermal dysplasia and pituitary gland involvement than NFKB1LOF patients. Most NFKB1LOF and p52LOF/IκBδGOF cases showed low CD19 + B cells, with p52LOF/IκBδGOF having more cases of this type. Low memory B cells were more common in p52LOF/IκBδGOF patients. CONCLUSIONS: Patients with NFKB2 mutations, particularly p52LOF/IκBδGOF, are at higher risk of viral infections, pituitary gland involvement, and ectodermal dysplasia compared to patients with NFKB1LOF mutations. Genetic testing is essential to resolve the initial complexity and confusion surrounding clinical and immunological features. Emphasizing the significance of functional assays in determining the probability of correlations between mutations and immunological and clinical characteristics of patients is crucial.

Allergies and risk of head and neck cancer: a case-control study.

Although the relationship between allergies and cancer has been investigated extensively, the role of allergies in head and neck cancer (HNC) appears less consistent. It is unclear whether allergies can independently influence the risk of HNC in the presence of substantial environmental risk factors, including consumption of alcohol, betel quid, and cigarettes. This study aims to find this association. We examined the relationship between allergies and HNC risk in a hospital-based case-control study with 300 cases and 375 matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals, controlling for age, sex, tobacco smoking and opium usage history, alcohol consumption, and socioeconomic status. Our study showed a significant reduction in the risk of HNC associated with allergy symptoms after adjusting for confounders. The risk of HNC was greatly reduced among those with any type of allergy (OR 0.42, 95% CI 0.28, 0.65). The ORs were considerably reduced by 58-88% for different kinds of allergies. The risk of HNC reduction was higher in allergic women than in allergic men (71% vs. 49%). Allergies play an influential role in the risk of HNC development. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are necessary to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help to devise effective strategies to reduce and treat HNC.

The Role of Alpha-Synuclein in Neurodevelopmental Diseases.

Neurodevelopmental disorders are a group of diseases with cognitive, motor, and emotional development deficits. Alpha-synuclein (α-syn) is a synaptic protein involved in transmission and neurodevelopment. This protein was previously shown to be associated with several disorders, including Parkinson's disease. Furthermore, a close link between neurodevelopmental disorders and Parkinson's has also been found. Changes in synaptic function have been noticed in neurodevelopmental disorders, including autism spectrum disorder. Impaired neurogenesis and related cognitive problems have been associated with altered expression of α-syn. Various studies reported α-syn in different body fluids and tissues such as blood and serum. Alpha-synuclein can help in better understanding the pathogenesis of neurodevelopmental diseases and facilitating their early diagnosis. This review aims to go over the recent advances in the role of α-syn in the pathophysiology of neurodevelopmental disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, and motor and social impairment, and its value as a diagnostic biomarker.

The multidisciplinary approach to diagnosing inborn errors of immunity: a comprehensive review of discipline-based manifestations.

INTRODUCTION: Congenital immunodeficiency is named primary immunodeficiency (PID), and more recently inborn errors of immunity (IEI). There are more than 485 conditions classified as IEI, with a wide spectrum of clinical and laboratory manifestations. AREAS COVERED: Regardless of the developing knowledge of IEI, many physicians do not think of IEI when approaching the patient's complaint, which leads to delayed diagnosis, misdiagnosis, serious infectious and noninfectious complications, permanent end-organ damage, and even death. Due to the various manifestations of IEI and the wide spectrum of associated conditions, patients refer to specialists in different disciplines of medicine and undergo - mainly symptomatic - treatments, and because IEI are not included in physicians' differential diagnosis, the main disease remains undiagnosed. EXPERT OPINION: A multidisciplinary approach may be a proper solution. Manifestations and the importance of a multidisciplinary approach in the diagnosis of main groups of IEI are discussed in this article.

The role of AMPK in pancreatic cancer: from carcinogenesis to treatment.

Pancreatic cancer has doubled over the previous two decades. Routine therapies are becoming incredibly resistant and failing to compensate for the burden caused by this aggressive neoplasm. As genetic susceptibility has always been a highlighted concern for this disease, identifying the molecular pathways involved in the survival and function of pancreatic cancer cells provides insight into its variant etiologies, one of which is the role of AMPK. This regulating factor of cell metabolism is crucial in the homeostasis and growth of the cell. Herein, we review the possible role of AMPK in pancreatic cancer while considering its leading effects on glycolysis and autophagy. Then, we assess the probable therapeutic agents that have resulted from the suggested pathways. Studying the underlying genetic changes in pancreatic cancer provides a chance to detect and treat patients suffering from advanced stages of the disease, and those who have given up their hope on conventional therapies can gain an opportunity to combat this cancer.

New insight into impact of humidity on direct air capture performance by SIFSIX-3-Cu MOF.

Removal of CO2 from air is one of the key human challenges in battling global warming. SIFSIX-3-Cu is a promising metal-organic framework (MOF) suggested for carbon capture even at low CO2 concentrations. However, the impact of humidity on its performance in direct air capture (DAC) is poorly understood. To evaluate the MOF performance for DAC application under humid conditions, we investigate the adsorption of H2O, CO2, and N2 using density functional theory (DFT), grand canonical Monte Carlo (GCMC), and molecular dynamics (MD) simulations. The simulation results show a higher tendency of SIFSIX-3-Cu towards H2O adsorption rather than CO2 (and N2). The results agree with the adsorption isotherms for the pure compounds from the Sips model. The extended Sips model shows 1.34 mmol g-1 CO2 adsorption at the atmospheric pressure and 298 K for the CO2/N2 mixture containing 400 ppm CO2, and low CO2 adsorption (less than 0.75 mmol g-1) at a low relative humidity (RH) of 20%. This finding highlights the efficiency of SIFSIX-3-Cu for DAC in dry air and the negative impact of humidity on the CO2 selective adsorption. Therefore, we suggest to consider the impairing of humidity effects when designing a SIFSIX-3-Cu-based CO2 separation process and removal of any water vapor before introduction of the air to SIFSIX-3-Cu.

The Cochrane risk of bias assessment tool 2 (RoB 2) versus the original RoB: A perspective on the pros and cons.

Background and Aims: Critical appraisal or risk of bias assessment is a fundamental part of systematic reviews that clarifies the degree to which included research articles are qualified and reliable. Version 2 of the Cochrane tool for assessing the risk of bias in randomized trials (RoB 2), the updated version of the first tool, was released in 2019. Here, we have compared these two versions of Cochrane risk of bias assessment tools and highlighted the pros and cons of RoB 2. Methods: Statistical analysis and methodology is not applicable to this article as no new data were created or analyzed in this study. Results: The overall approach in RoB 2 is that by answering some signaling questions after the specification of results, effects of interest, and sources of information, an overall judgment for the quality of each study is reached. Accordingly, in the original version of the Cochrane RoB tool, the judgment can be in three different conclusions, including low, unclear, and high risk of bias. The most prominent difference in bias domains is the removal of "other bias" domain being replaced by "overall bias" judgment. Also, the most common presentation types of Cochrane risk of bias assessments are the "summary" and "graph" which are generated by Review Manager, web-based applications, or packages in R software. Conclusion: The RoB 2 tool, compared to the original RoB, has improved and is the recommended version by the Cochrane Collaboration for quality assessment of randomized controlled trials. It is recommended to consider funding source, duration of follow-up, declaration of data availability, the status of baseline characteristics between groups, and sample size calculation methods in further revisions of the Cochrane risk of bias assessment tools.

Ferroptosis as a promising targeted therapy for triple negative breast cancer.

PURPOSE: Triple negative breast cancer (TNBC) is a challenging subtype characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Standard treatment options are limited, and approximately 45% of patients develop distant metastasis. Ferroptosis, a regulated form of cell death triggered by iron-dependent lipid peroxidation and oxidative stress, has emerged as a potential targeted therapy for TNBC. METHODS: This study utilizes a multifaceted approach to investigate the induction of ferroptosis as a therapeutic strategy for TNBC. It explores metabolic alterations, redox imbalance, and oncogenic signaling pathways to understand their roles in inducing ferroptosis, characterized by lipid peroxidation, reactive oxygen species (ROS) generation, and altered cellular morphology. Critical pathways such as Xc-/GSH/GPX4, ACSL4/LPCAT3, and nuclear factor erythroid 2-related factor 2 (NRF2) are examined for their regulatory roles in ferroptosis and their potential dysregulation contributing to cancer cell survival and resistance. RESULTS: Inducing ferroptosis has been shown to inhibit tumor growth, enhance the efficacy of conventional therapies, and overcome drug resistance in TNBC. Lipophilic antioxidants, GPX4 inhibitors, and inhibitors of the Xc- system have been demonstrated to be potential ferroptosis inducers. Additionally, targeting the NRF2 pathway and exploring other ferroptosis regulators, such as ferroptosis suppressor protein 1 (FSP1), and the PERK-eIF2α-ATF4-CHOP pathway, may offer novel therapeutic avenues. CONCLUSION: Further research is needed to understand the mechanisms, optimize therapeutic strategies, and evaluate the safety and efficacy of ferroptosis-targeted therapies in TNBC treatment. Overall, targeting ferroptosis represents a promising approach to improving treatment outcomes and overcoming the challenges posed by TNBC.

A viral attack on brain tumors: the potential of oncolytic virus therapy.

Managing malignant brain tumors remains a significant therapeutic hurdle that necessitates further research to comprehend their treatment potential fully. Oncolytic viruses (OVs) offer many opportunities for predicting and combating tumors through several mechanisms, with both preclinical and clinical studies demonstrating potential. OV therapy has emerged as a potent and effective method with a dual mechanism. Developing innovative and effective strategies for virus transduction, coupled with immune checkpoint inhibitors or chemotherapy drugs, strengthens this new technique. Furthermore, the discovery and creation of new OVs that can seamlessly integrate gene therapy strategies, such as cytotoxic, anti-angiogenic, and immunostimulatory, are promising advancements. This review presents an overview of the latest advancements in OVs transduction for brain cancer, focusing on the safety and effectiveness of G207, G47Δ, M032, rQNestin34.5v.2, C134, DNX-2401, Ad-TD-nsIL12, NSC-CRAd-S-p7, TG6002, and PVSRIPO. These are evaluated in both preclinical and clinical models of various brain tumors.

Circulating miRNA and circulating tumor DNA application as liquid biopsy markers in gastric cancer.

Liquid biopsy has been investigated as a novel method to overcome the numerous challenges in gastric cancer (GC) management. This non-invasive, feasible, and easy-to-repeat method has been shown to be cost-effective and capable of increasing diagnostic sensitivity and prognostic assessment. Additionally, it is potentially accurate to aid decision-making and personalized treatment planning. MicroRNA (miRNA) and circulating tumor DNA (ctDNA) markers can enhance GC management in various aspects, including diagnosis (mainly earlier diagnosis and the ability to perform population-based screening), prognosis (more precise stratification of prognosis), and treatment (including more accurate prediction of treatment response and earlier detection of resistance to the treatment). Concerning the treatment-related application, miRNAs' mimics and antagonists (by using two main strategies of restoring tumor suppressor miRNAs and inhibiting oncogene miRNAs) have been shown to be effective therapeutic agents. However, these need to be further validated in clinical trials. Furthermore, novel delivery systems, such as lipid-based vectors, polymeric-based vectors, and exosome-based delivery, have been developed to enhance the performance of these agents. Moreover, this paper explores the current detection and measuring methods for these markers. These approaches are categorized into direct methods (e.g., Chem-NAT, HTG EdgeSeq, and Multiplex Circulating Fireplex) and indirect methods (e.g., Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), qPCR, microarray, and NGS) for miRNA detection. For ctDNA measurement, main core technologies like NGS, digital PCR, real-time PCR, and mass spectrometry are suggested.

Machine learning and artificial intelligence within pediatric autoimmune diseases: applications, challenges, future perspective.

INTRODUCTION: Autoimmune disorders affect 4.5% to 9.4% of children, significantly reducing their quality of life. The diagnosis and prognosis of autoimmune diseases are uncertain because of the variety of onset and development. Machine learning can identify clinically relevant patterns from vast amounts of data. Hence, its introduction has been beneficial in the diagnosis and management of patients. AREAS COVERED: This narrative review was conducted through searching various electronic databases, including PubMed, Scopus, and Web of Science. This study thoroughly explores the current knowledge and identifies the remaining gaps in the applications of machine learning specifically in the context of pediatric autoimmune and related diseases. EXPERT OPINION: Machine learning algorithms have the potential to completely change how pediatric autoimmune disorders are identified, treated, and managed. Machine learning can assist physicians in making more precise and fast judgments, identifying new biomarkers and therapeutic targets, and personalizing treatment strategies for each patient by utilizing massive datasets and powerful analytics.

The role of extracellular vesicles in immune cell exhaustion and resistance to immunotherapy.

INTRODUCTION: Extracellular vesicles (EVs) are membrane-bound nanoparticles for intercellular communication. Subtypes of EVs, namely exosomes and microvesicles transfer diverse, bioactive cargo to their target cells and eventually interfere with immune responses. Despite being a promising approach, cancer immunotherapy currently faces several challenges including immune resistance. EVs secreted from various sources in the tumor microenvironment provoke immune cell exhaustion and lower the efficacy of immunological treatments, such as CAR T cells and immune checkpoint inhibitors. AREAS COVERED: This article goes through the mechanisms of action of various types of EVs in inhibiting immune response and immunotherapies, and provides a comprehensive review of EV-based treatments. EXPERT OPINION: By making use of the distinctive features of EVs, natural or modified EVs are innovatively utilized as novel cancer therapeutics. They are occasionally coupled with currently established treatments to overcome their inadequacies. Investigating the properties and interactions of EVs and EV-based treatments is crucial for determining future steps in cancer therapeutics.

The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk.

Extracellular vesicles (EVs) are lipid bilayer structures released by all cells and widely distributed in all biological fluids. EVs are implicated in diverse physiopathological processes by orchestrating cell-cell communication. Colorectal cancer (CRC) is one of the most common cancers worldwide, with metastasis being the leading cause of mortality in CRC patients. EVs contribute significantly to the advancement and spread of CRC by transferring their cargo, which includes lipids, proteins, RNAs, and DNAs, to neighboring or distant cells. Besides, they can serve as non-invasive diagnostic and prognostic biomarkers for early detection of CRC or be harnessed as effective carriers for delivering therapeutic agents. Autophagy is an essential cellular process that serves to remove damaged proteins and organelles by lysosomal degradation to maintain cellular homeostasis. Autophagy and EV release are coordinately activated in tumor cells and share common factors and regulatory mechanisms. Although the significance of autophagy and EVs in cancer is well established, the exact mechanism of their interplay in tumor development is obscure. This review focuses on examining the specific functions of EVs in various aspects of CRC, including progression, metastasis, immune regulation, and therapy resistance. Further, we overview emerging discoveries relevant to autophagy and EVs crosstalk in CRC.

Improving the estimation accuracy of confined vapor-liquid equilibria by fine-tuning the pure component parameter in the PC-SAFT equation of state.

We propose a thermodynamic model that combines the Young-Laplace equation and perturbed chain-statistical associating fluid theory (PC-SAFT) equation of state to estimate capillary condensation pressure in microporous and mesoporous sorbents. We adjust the PC-SAFT dispersion-energy parameter when the pore size becomes comparable to the molecular dimension. This modelling framework is applied to diverse systems containing associating and non-associating gases, various sorbents, and a wide range of temperatures. Our simulation results show that under extreme confinement, a higher value of the dispersion-energy parameter (ε) is required. Furthermore, using the experimental saturation pressure data for 18 different associating and non-associating confined fluids, we find that the shift in the PC-SAFT dispersion energy correlates with the ratio of the sorbent mean pore size to the PC-SAFT segment size (rp/σ). By fitting to the capillary condensation data, the relative deviation between the confined and bulk PC-SAFT dispersion energy parameter is only 0.1% at rp/σ = 15; however, this deviation starts to increase exponentially as rp/σ decreases. For a sorbent with large pores, when rp/σ > 15, the capillary condensation pressure results from our model are similar to the predictions from the Kelvin equation. Using a dataset containing 235 saturation pressure data points composed of 18 pure gases and 4 binary mixtures, the overall AARD% from our model is 12.26%, which verifies the good accuracy of our model. Because the mean sorbent pore radius (rp), the PC-SAFT energy parameter (ε), and segment size (σ) are known a priori, our model estimates the corrected energy parameter for small pores and, thus, extends its applicability.

Role of long non-coding RNAs in cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Cholangiocarcinoma (CCA), as a rare malignancy of the biliary tree, has a poor prognosis most of the time. CCA is highly epigenetically regulated and several long non-coding RNAs (lncRNA) have been investigated to have a diagnostic and prognostic role in CCA. The current study aimed to assess the studies finding relevant lncRNAs in CCA systematically. METHODS: International databases, including PubMed, Cochrane Library, and Embase, were comprehensively searched in order to identify studies investigating any lncRNA in CCA. After screening by title/abstract and full-text, necessary data were extracted. Random-effect meta-analysis was performed for pooling the areas under the curve (AUCs), specificity, and sensitivity of lncRNAs for the diagnosis of CCA. RESULTS: A total of 33 studies were chosen to be included in the final analysis, comprised of 2677 patients. Meta-analysis of AUCs for evaluation of CCA resulted in pooled AUC of 0.79 (95% CI: 0.75-0.82; I2 = 69.11, p < .01). Additionally, overall sensitivity of 0.80 (95% CI 0.75-0.84) and specificity of 0.77 (95% CI: 0.68-0.84) were observed. Measurement of lncRANs in the assessment of CCA also improved overall survival significantly (effect size 1.61, 95% CI: 1.39-1.82). A similar result was found for progression-free survival (effect size 1.57, 95% CI: 1.20-1.93). CONCLUSION: Based on our findings, lncRNAs showed promising results as biomarkers in the diagnosis of CCA since they had acceptable sensitivity and specificity, in addition to the fact that improved survival in this poor prognosis cancer. Further studies might be needed to address this issue and find the best clinically useful lncRNA.

The role of long noncoding RNAs in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a poor prognosis leading to death. The diagnosis and treatment of ALS are inherently challenging due to its complex pathomechanism. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides involved in different cellular processes, incisively gene expression. In recent years, more studies have been conducted on lncRNA classes and interference in different disease pathologies, showing their promising contribution to diagnosing and treating neurodegenerative diseases. In this review, we discussed the role of lncRNAs like NEAT1 and C9orf72-as in ALS pathogenesis mechanisms caused by mutations in different genes, including TAR DNA-binding protein-43 (TDP-43), fused in sarcoma (FUS), superoxide dismutase type 1 (SOD1). NEAT1 is a well-established lncRNA in ALS pathogenesis; hence, we elaborate on its involvement in forming paraspeckles, stress response, inflammatory response, and apoptosis. Furthermore, antisense lncRNAs (as-lncRNAs), a key group of transcripts from the opposite strand of genes, including ZEB1-AS1 and ATXN2-AS, are discussed as newly identified components in the pathology of ALS. Ultimately, we review the current standing of using lncRNAs as biomarkers and therapeutic agents and the future vision of further studies on lncRNA applications.