Regulation and postsynaptic binding of neurexins — drug targets for neurodevelopmental and neuropsychiatric disorders

Ding, Yicheng; Howard, Linda; Gallagher, Louise; Shen, Sanbing

doi:10.1007/s11515-015-1363-1

Cited by 2 publications

(2 citation statements)

References 125 publications

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“…Identifying likely genetic etiologies of ASD is the first major step in creating gene editing for this disease. In addition to genetic therapies, targeted drug therapies for NRXN1 related molecules may be useful in treating the associated clinical symptoms [108]. These therapies include RNAi, protein replacement, small molecule therapy, and chaperone therapy [109][110][111][112][113][114].…”

Section: Discussionmentioning

confidence: 99%

Landscape of NRXN1 Gene Variants in Phenotypic Manifestations of Autism Spectrum Disorder: A Systematic Review

Cooper,

Mittal,

Sangadi

et al. 2024

JCM

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Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication challenges and repetitive behaviors. Recent research has increasingly focused on the genetic underpinnings of ASD, with the Neurexin 1 (NRXN1) gene emerging as a key player. This comprehensive systematic review elucidates the contribution of NRXN1 gene variants in the pathophysiology of ASD. Methods: The protocol for this systematic review was designed a priori and was registered in the PROSPERO database (CRD42023450418). A risk of bias analysis was conducted using the Joanna Briggs Institute (JBI) critical appraisal tool. We examined various studies that link NRXN1 gene disruptions with ASD, discussing both the genotypic variability and the resulting phenotypic expressions. Results: Within this review, there was marked heterogeneity observed in ASD genotypic and phenotypic manifestations among individuals with NRXN1 mutations. The presence of NRXN1 mutations in this population emphasizes the gene’s role in synaptic function and neural connectivity. Conclusion: This review not only highlights the role of NRXN1 in the pathophysiology of ASD but also highlights the need for further research to unravel the complex genetic underpinnings of the disorder. A better knowledge about the multifaceted role of NRXN1 in ASD can provide crucial insights into the neurobiological foundations of autism and pave the way for novel therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Landscape of NRXN1 Gene Variants in Phenotypic Manifestations of Autism Spectrum Disorder: A Systematic Review

Cooper,

Mittal,

Sangadi

et al. 2024

JCM

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“…These genes include SH3 and multiple ankyrin repeat domains 3 ( SHANK3 ), neurexins ( NRXN s) and neuroligins ( NLGNs ) which encode proteins involved in synaptic transmission and plasticity [ 13 ]. Neurexins are pre-synaptic cell adhesion molecules encoded by NRXN 1, 2 and 3 genes, while NLGN s are post-synaptic cell adhesion molecules encoded by NLGN 1, 2, 3 and 4 [ 13 , 14 ]. SHANK3 , NRXN1 , NRXN2 , NLGN1 and NLGN2 are candidate NDD susceptibility genes.…”

Section: Introductionmentioning

confidence: 99%

Mycobacterium tuberculosis-Induced Maternal Immune Activation Promotes Autism-Like Phenotype in Infected Mice Offspring

Manjeese

Mvubu

Steyn

et al. 2021

IJERPH

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The maternal system’s exposure to pathogens during pregnancy influences fetal brain development causing a persistent inflammation characterized by elevated pro-inflammatory cytokine levels in offspring. Mycobacterium tuberculosis (Mtb) is a global pathogen that causes tuberculosis, a pandemic responsible for health and economic burdens. Although it is known that maternal infections increase the risk of autism spectrum disorder (ASD), it is not known whether Mtb infection is sufficient to induce ASD associated behaviors, immune dysregulation and altered expression of synaptic regulatory genes. The current study infected pregnant Balb/c mice with Mtb H37Rv and valproic acid (VPA) individually and in combination. Plasma cytokine profiles were measured in offspring using the Bio-plex Th17 pro mouse cytokine panel. Mtb infection increased plasma interleukin (IL)-6 and IL-17A, while tumor necrosis factor alpha (TNF-α), interferon (IFN)-γ and IL-1β were reduced when compared with saline. Mtb-induced maternal immune activation (MIA) offspring displayed increased grooming behavior. The study also revealed dysregulation in gene expression of synaptic molecules in the cerebellum. MIA rescued the VPA-induced effects on self-grooming and social interaction behaviors. Our finding therefore highlights a potential role of Mtb as a MIA agent that can potentially contribute to ASD.

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Regulation and postsynaptic binding of neurexins — drug targets for neurodevelopmental and neuropsychiatric disorders

Cited by 2 publications

References 125 publications

Landscape of NRXN1 Gene Variants in Phenotypic Manifestations of Autism Spectrum Disorder: A Systematic Review

Landscape of NRXN1 Gene Variants in Phenotypic Manifestations of Autism Spectrum Disorder: A Systematic Review

Mycobacterium tuberculosis-Induced Maternal Immune Activation Promotes Autism-Like Phenotype in Infected Mice Offspring

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