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Background: The aim of the study was to assess a panel of promising biomarkers for their ability to improve diagnosis of sporadic amyotrophic lateral sclerosis (ALS).Methods: Forty patients with sporadic ALS and 40 controls with other neurological diseases were evaluated. Levels of phosphorylated neurofilament heavy chain (pNfH), S100-β, cystatin C, and chitotriosidase (CHIT) in cerebrospinal fluid were assayed using two-site solid-phase sandwich ELISA.Results: Patients with sporadic ALS showed higher levels of pNfH and CHIT than controls, but lower levels of cystatin C. Multivariate logistic regression that adjusted for patient age and sex identified significant associations between sporadic ALS and levels of pNfH, CHIT and cystatin C. Levels of pNfH correlated positively with rate of progression and decline based on the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Based on receiver operating curve analysis, a pNfH cut-off of 437 ng/L discriminated patients from controls with a sensitivity of 97.3 % and specificity of 83.8 %. A CHIT cut-off of 1593.779 ng/L discriminated patients from controls with a sensitivity of 83.8 % and specificity of 81.1 %. Combining the two biomarkers gave a sensitivity of 83.8 % and specificity of 91.9 %.Conclusions: Levels of pNfH in cerebrospinal fluid may be a reliable biomarker for diagnosing ALS, and combining this biomarker with levels of CHIT may improve diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to assess a panel of promising biomarkers for their ability to improve diagnosis of sporadic amyotrophic lateral sclerosis (ALS)., Methods: Forty patients with sporadic ALS and 40 controls with other neurological diseases were evaluated. Levels of phosphorylated neurofilament heavy chain (pNfH), S100-β, cystatin C, and chitotriosidase (CHIT) in cerebrospinal fluid were assayed using two-site solid-phase sandwich ELISA., Results: Patients with sporadic ALS showed higher levels of pNfH and CHIT than controls, but lower levels of cystatin C. Multivariate logistic regression that adjusted for patient age and sex identified significant associations between sporadic ALS and levels of pNfH, CHIT and cystatin C. Levels of pNfH correlated positively with rate of progression and decline based on the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Based on receiver operating curve analysis, a pNfH cut-off of 437 ng/L discriminated patients from controls with a sensitivity of 97.3 % and specificity of 83.8 %. A CHIT cut-off of 1593.779 ng/L discriminated patients from controls with a sensitivity of 83.8 % and specificity of 81.1 %. Combining the two biomarkers gave a sensitivity of 83.8 % and specificity of 91.9 %., Conclusions: Levels of pNfH in cerebrospinal fluid may be a reliable biomarker for diagnosing ALS, and combining this biomarker with levels of CHIT may improve diagnostic accuracy.

Background: Beta-catenin has two major functions: coordinating cell-cell adhesion by interacting with cadherin in cadherin junction formation pathway; and regulating gene expression through Wnt signaling pathway. Accomplishing these two functions requires synergistic action of various sequential regions of the same beta-Catenin molecule, including the N-terminal tail, the middle armadillo domain, and the C-terminal tail. Although the middle armadillo domain is the major functional unit of beta-Catenin, the involvement of tails in the regulation of interaction between beta-Catenin and its partners has been well observed. Nonetheless, the regulatory processes of both tails are still elusive. In addition, it is interesting to note that the three sequential regions have different structural features: The middle armadillo domain is structured, but both N- and C-terminal tails are disordered. This observation leads to another important question on the functions and mechanisms of disordered tails, which is also largely unknown., Results: In this study, we focused on the characterization of sequential, structural, and functional features of the disordered tails of beta-Catenin. We identified multiple functional motifs and conserved sequence motifs in the disordered tails, discovered the correlation between cancer-associated mutations and functional motifs, explored the abundance of protein intrinsic disorder in the interactomes of beta-Catenin, and elaborated a working model on the regulatory roles of disordered tails in the functional pathways of beta-Catenin., Conclusion: Disordered tails of beta-Catenin contain multiple functional motifs. These motifs interact with each other and the armadillo domain of beta-catenin to regulate the function of beta-Catenin in both cadherin junction formation pathway and Wnt signaling pathway.