Do Low Serum UCH-L1 and TDP-43 Levels Indicate Disturbed Ubiquitin- Proteosome System in Autism Spectrum Disorder?

Çetin, İhsan; Tezdig, Ihsan; Tarakçıoğlu, Mahmut Cem; Kadak, Muhammed Tayyib; Demirel, Ömer Faruk; Özer, Ömer Faruk; Erdoğan, Fırat; Doğangün, Burak

doi:10.5152/npa.2017.14873

Cited by 4 publications

(7 citation statements)

References 45 publications

(41 reference statements)

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“…Low levels of TDP-43 were observed in children with autism [72]. It is thought based on this study, that during early development low levels of TDP-43 may have contributed to the dysfunction of the ubiquitin-proteasome system [72]. As previously discussed, low levels of TDP-43 lead to dysfunction in the ubiquitin-proteasome system (UPS).…”

Section: Autism Spectrum Disorder (Asd)supporting

confidence: 59%

“…In a preliminary study, TDP-43 levels were observed in children with and without autism [72]. Low levels of TDP-43 were observed in children with autism [72]. It is thought based on this study, that during early development low levels of TDP-43 may have contributed to the dysfunction of the ubiquitin-proteasome system [72].…”

Section: Autism Spectrum Disorder (Asd)mentioning

confidence: 54%

“…The disorder ranges from behavioral and communicative deficits. In a preliminary study, TDP-43 levels were observed in children with and without autism [72]. Low levels of TDP-43 were observed in children with autism [72].…”

Section: Autism Spectrum Disorder (Asd)mentioning

confidence: 89%

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Transactivation Response DNA-Binding Protein of 43 (TDP-43) and Glial Cell Roles in Neurological Disorders

Hussain¹,

Djurin²,

Rodríguez³

et al. 2022

Cureus

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The trans-activation response DNA-binding protein of 43kDa (TDP-43) is involved in the pathogenesis of multiple brain disorders. As scientists are unraveling TDP-43 function and its impact on various diseases, we have begun to subcategorize them into TDP-43 proteinopathies. Furthermore, glial cell dysfunction contributes to various disorders, and TDP-43 is involved with glial cells via multiple pathways (direct or indirect) that aggravate the pathophysiology of such disorders. We are only now discovering and understanding the vast and diverse roles TDP-43 plays on neuronal cells and its effects on gliosis and neurodegenerative pathologies. It has multiple roles: mRNA maturation and splicing, transporting and maintaining mRNA stability, a component of stress granules and ubiquitination of dysfunctional or misfolded proteins, transcription of microtubule "Futsch" protein, and a role in maintaining synapse integrity and possibly more as we continue to research and uncover the labyrinth of the neuronal network. TDP-43 could also have a detrimental impact on glial cell activation and pathophysiology in diseases where TDP-43 is associated with its pathogenesis. We will review the pathophysiology of various neurological disorders that are associated with the alteration of the TDP-43 levels along with glial cell activation. Further, multiple diseases have glial cell participation in the pathogenesis, and the role of TDP-43 has not yet been investigated. We, therefore, explore those disorders in the context of both TDP-43 and glial cells involvement. This step will enhance the understanding of neurodegeneration where further research could prompt curative modalities with the advancement of technology.

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Section: Autism Spectrum Disorder (Asd)supporting

confidence: 59%

Section: Autism Spectrum Disorder (Asd)mentioning

confidence: 54%

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Transactivation Response DNA-Binding Protein of 43 (TDP-43) and Glial Cell Roles in Neurological Disorders

Hussain¹,

Djurin²,

Rodríguez³

et al. 2022

Cureus

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“…SEZ6L ( 22) is a candidate gene for autism. Low levels of ubiquitin carboxy-terminal hydrolase isoenzyme L1 (UCHL1) is associated with ubiquitination interference in autism (23). Beta-2-glycoprotein 1 (APOH) was reported to be elevated in the plasma of patients with autism compared with that of control subjects (24).…”

Section: Discussionmentioning

confidence: 99%

Urinary proteome profiling for children with autism using data-independent acquisition proteomics

Meng¹,

Huan²,

Gao³

2021

Transl Pediatr

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Background: Autism is a complex neurodevelopmental disorder. Objective and reliable biomarkers are crucial for the clinical diagnosis of autism. Urine can accumulate early changes of the whole body and is a sensitive source for disease biomarkers. Methods:The data-independent acquisition (DIA) strategy was used to identify differential proteins in the urinary proteome between autistic and non-autistic children aged 3-7 years. Receiver operating characteristic (ROC) curves were developed to evaluate the diagnostic performance of differential proteins.Results: A total of 118 differential proteins were identified in the urine between autistic and non-autistic children, of which 18 proteins were reported to be related to autism. Randomized grouping statistical analysis indicated that 91.5% of the differential proteins were reliable. Functional analysis revealed that some differential proteins were associated with axonal guidance signaling, endocannabinoid developing neuron pathway, synaptic long-term depression, agrin interactions at neuromuscular junction, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling and synaptogenesis signaling pathway. The combination of cadherin-related family member 5 (CDHR5) and vacuolar protein sorting-associated protein 4B (VPS4B) showed the best discriminative performance between autistic and non-autistic children with an area under the curve (AUC) value of 0.987. Conclusions:The urinary proteome could distinguish between autistic children and non-autistic children.This study will provide a promising approach for future biomarker research of neuropsychiatric disorders.

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“…From the perspective of pathology, SD has been reported to be predominantly associated with DNA-binding protein 43 (TDP-43) [ 35 ]. While the background pathology of ASD has not yet been elucidated, Cetin et al reported that the mean serum TDP-43 levels in children with ASD were lower than those of healthy control children [ 36 ]. These findings highlight the possibility that functional abnormalities of TDP-43 may be involved in the development of behavioral symptoms that are common to both SD and ASD.…”

Section: Discussionmentioning

confidence: 99%

Clinical features of behavioral symptoms in patients with semantic dementia: Does semantic dementia cause autistic traits?

et al. 2021

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Objective To investigate the behavioral characteristics of semantic dementia (SD) using an instrument originally developed for patients with autism spectrum disorder. Methods The behavioral symptoms of 20 patients with SD and 20 patients with Alzheimer’s disease (AD) in both the preclinical state and the dementia state were evaluated using the Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS). Results The SD group showed high prevalence in four behaviors related to stereotypy and social impairment: eating very few food items, selfishness, difficulty in recognizing others’ feeling and thoughts, and interpreting language literally. Scores on the PARS short version, which is sensitive for diagnosis of autism spectrum disorder, were significantly higher in the dementia state than in the preclinical state in both the SD (11.5 ± 6.0 and 1.7 ± 2.5, respectively; t (19) = 6.7, p < 0.001) and AD (6.9 ± 4.6 and 1.7 ± 2.0, respectively; t (19) = 5.1, p < 0.001) groups. PARS short version scores after dementia onset increased in both the SD and AD groups, although the increase was significantly larger in the SD group (F = 5.6, p = 0.023). Additionally, a significantly higher rate of patients exceeded the cutoff score for autism diagnosis in the dementia state in the SD group (75%) than in the AD group (40%; χ2 = 5.0, p = 0.025). PARS scores in the dementia state were significantly correlated with illness duration (r = 0.46, p = 0.04) and Mini-Mental State Examination scores (r = −0.75, p < 0.001) in the SD group only. Conclusions Although SD and autism spectrum disorder are etiologically distinct diseases, patients with semantic dementia behave like those with autism spectrum disorder. Our findings suggest the symptomatic similarity of the two disorders.

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Do Low Serum UCH-L1 and TDP-43 Levels Indicate Disturbed Ubiquitin- Proteosome System in Autism Spectrum Disorder?

Cited by 4 publications

References 45 publications

Transactivation Response DNA-Binding Protein of 43 (TDP-43) and Glial Cell Roles in Neurological Disorders

Transactivation Response DNA-Binding Protein of 43 (TDP-43) and Glial Cell Roles in Neurological Disorders

Urinary proteome profiling for children with autism using data-independent acquisition proteomics

Clinical features of behavioral symptoms in patients with semantic dementia: Does semantic dementia cause autistic traits?

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