CD38 and MGluR1 as possible signaling molecules involved in epileptogenesis: A potential role for NAD+ homeostasis

Khodaverdian, Shima; Dashtban-Moghadam, Elahe; Dabirmanesh, Bahareh; Mirnajafi‐Zadeh, Javad; Taleb, Mohammad; Khajeh, Khosro; Fathollahi, Yaghoub

doi:10.1016/j.brainres.2021.147509

Cited by 7 publications

(2 citation statements)

References 52 publications

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“…Five feature genes, namely CD38, FAIM2, IL1B, PAWR, and S100A8, were identified as diagnostic biomarkers for epilepsy subtyping, forming the basis for constructing a disease classification model. Notably, CD38, a transmembrane glycoprotein, emerged as a key player in epilepsy pathogenesis due to its involvement in NAD+ degradation and intracellular calcium ion balance ( Guerreiro et al, 2020 ; Khodaverdian et al, 2021 ). Targeting CD38 presents a potential therapeutic avenue.…”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes significantly linked to temporal lobe epilepsy and apoptosis via bioinformatics analysis

Wang,

Ren,

et al. 2024

Front. Mol. Neurosci.

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BackgroundEpilepsy stands as an intricate disorder of the central nervous system, subject to the influence of diverse risk factors and a significant genetic predisposition. Within the pathogenesis of temporal lobe epilepsy (TLE), the apoptosis of neurons and glial cells in the brain assumes pivotal importance. The identification of differentially expressed apoptosis-related genes (DEARGs) emerges as a critical imperative, providing essential guidance for informed treatment decisions.MethodsWe obtained datasets related to epilepsy, specifically GSE168375 and GSE186334. Utilizing differential expression analysis, we identified a set of 249 genes exhibiting significant variations. Subsequently, through an intersection with apoptosis-related genes, we pinpointed 16 genes designated as differentially expressed apoptosis-related genes (DEARGs). These DEARGs underwent a comprehensive array of analyses, including enrichment analyses, biomarker selection, disease classification modeling, immune infiltration analysis, prediction of miRNA and transcription factors, and molecular docking analysis.ResultsIn the epilepsy datasets examined, we successfully identified 16 differentially expressed apoptosis-related genes (DEARGs). Subsequent validation in the external dataset GSE140393 revealed the diagnostic potential of five biomarkers (CD38, FAIM2, IL1B, PAWR, S100A8) with remarkable accuracy, exhibiting an impressive area under curve (AUC) (The overall AUC of the model constructed by the five key genes was 0.916, and the validation set was 0.722). Furthermore, a statistically significant variance (p < 0.05) was observed in T cell CD4 naive and eosinophil cells across different diagnostic groups. Exploring interaction networks uncovered intricate connections, including gene-miRNA interactions (164 interactions involving 148 miRNAs), gene-transcription factor (TF) interactions (22 interactions with 20 TFs), and gene-drug small molecule interactions (15 interactions involving 15 drugs). Notably, IL1B and S100A8 demonstrated interactions with specific drugs.ConclusionIn the realm of TLE, we have successfully pinpointed noteworthy differentially expressed apoptosis-related genes (DEARGs), including CD38, FAIM2, IL1B, PAWR, and S100A8. A comprehensive understanding of the implications associated with these identified genes not only opens avenues for advancing our comprehension of the underlying pathophysiology but also bears considerable potential in guiding the development of innovative diagnostic methodologies and therapeutic interventions for the effective management of epilepsy in the future.

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Section: Discussionmentioning

confidence: 99%

Identification of hub genes significantly linked to temporal lobe epilepsy and apoptosis via bioinformatics analysis

Wang,

Ren,

et al. 2024

Front. Mol. Neurosci.

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“…Moreover, the expression level of the gene-encoding mGluR1 (one of CD38 metabolite related proteins) significantly changes then. It means that changes in the expression of the CD38/cADPR signaling pathway may be crucial in epileptogenesis [ 182 ].…”

Section: Cd38 Outside Hematologymentioning

confidence: 99%

Targeting CD38 in Neoplasms and Non-Cancer Diseases

Szlasa

Czarny

Sauer

et al. 2022

Cancers

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CD38 is a myeloid antigen present both on the cell membrane and in the intracellular compartment of the cell. Its occurrence is often enhanced in cancer cells, thus making it a potential target in anticancer therapy. Daratumumab and isatuximab already received FDA approval, and novel agents such as MOR202, TAK079 and TNB-738 undergo clinical trials. Also, novel therapeutics such as SAR442085 aim to outrank the older antibodies against CD38. Multiple myeloma and immunoglobulin light-chain amyloidosis may be effectively treated with anti-CD38 immunotherapy. Its role in other hematological malignancies is also important concerning both diagnostic process and potential treatment in the future. Aside from the hematological malignancies, CD38 remains a potential target in gastrointestinal, neurological and pulmonary system disorders. Due to the strong interaction of CD38 with TCR and CD16 on T cells, it may also serve as the biomarker in transplant rejection in renal transplant patients. Besides, CD38 finds its role outside oncology in systemic lupus erythematosus and collagen-induced arthritis. CD38 plays an important role in viral infections, including AIDS and COVID-19. Most of the undergoing clinical trials focus on the use of anti-CD38 antibodies in the therapy of multiple myeloma, CD19- B-cell malignancies, and NK cell lymphomas. This review focuses on targeting CD38 in cancer and non-cancerous diseases using antibodies, cell-based therapies and CD38 inhibitors. We also provide a summary of current clinical trials targeting CD38.

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Research progress on the role of inflammatory mediators in the pathogenesis of epilepsy

Yu,

Sun

2024

Ibrain

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Epilepsy is an abnormal neurologic disorder distinguished by the recurrent manifestation of seizures, and the precise underlying mechanisms for its development and progression remain uncertain. In recent years, the hypothesis that inflammatory mediators and corresponding pathways contribute to seizures has been supported by experimental results. The potential involvement of neuroinflammation in the development of epilepsy has garnered growing interest. This review centers attention on the involvement of inflammatory mediators in the emergence and progression of epilepsy within recent years, focusing on both clinical research and animal models, to enhance comprehension of the intricate interplay between brain inflammation and epileptogenesis.

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CD38 and MGluR1 as possible signaling molecules involved in epileptogenesis: A potential role for NAD+ homeostasis

Cited by 7 publications

References 52 publications

Identification of hub genes significantly linked to temporal lobe epilepsy and apoptosis via bioinformatics analysis

Identification of hub genes significantly linked to temporal lobe epilepsy and apoptosis via bioinformatics analysis

Targeting CD38 in Neoplasms and Non-Cancer Diseases

Research progress on the role of inflammatory mediators in the pathogenesis of epilepsy

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