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Protein engineering alters the polypeptide chain to obtain a novel protein with improved functional properties. This field constantly evolves with advanced in silico tools and techniques to design novel proteins and peptides. Rational incorporating mutations, unnatural amino acids, and post-translational modifications increases the applications of engineered proteins and peptides. It aids in developing drugs with maximum efficacy and minimum side effects. Currently, the engineering of peptides is gaining attention due to their high stability, binding specificity, less immunogenic, and reduced toxicity properties. Engineered peptides are potent candidates for drug development due to their high specificity and low cost of production compared with other biologics, including proteins and antibodies. Therefore, understanding the current perception of designing and engineering peptides with the help of currently available in silico tools is crucial. This review extensively studies various in silico tools available for protein engineering in the prospect of designing peptides as therapeutics, followed by in vitro aspects. Moreover, a discussion on the chemical synthesis and purification of peptides, a case study, and challenges are also incorporated.
Protein engineering alters the polypeptide chain to obtain a novel protein with improved functional properties. This field constantly evolves with advanced in silico tools and techniques to design novel proteins and peptides. Rational incorporating mutations, unnatural amino acids, and post-translational modifications increases the applications of engineered proteins and peptides. It aids in developing drugs with maximum efficacy and minimum side effects. Currently, the engineering of peptides is gaining attention due to their high stability, binding specificity, less immunogenic, and reduced toxicity properties. Engineered peptides are potent candidates for drug development due to their high specificity and low cost of production compared with other biologics, including proteins and antibodies. Therefore, understanding the current perception of designing and engineering peptides with the help of currently available in silico tools is crucial. This review extensively studies various in silico tools available for protein engineering in the prospect of designing peptides as therapeutics, followed by in vitro aspects. Moreover, a discussion on the chemical synthesis and purification of peptides, a case study, and challenges are also incorporated.
BackgroundAccumulating evidence suggested that Alzheimer’s disease (AD) was associated with altered gut microbiota. However, the relationships between gut microbiota and specific cognitive domains of AD patients have yet been fully elucidated. The aim of this study was to explore microbial signatures associated with global cognition and specific cognitive domains in AD patients and to determine their predictive value as biomarkers.MethodsA total of 64 subjects (18 mild AD, 23 severe AD and 23 healthy control) were recruited in the study. 16 s rDNA sequencing was performed for the gut bacteria composition, followed by liquid chromatography electrospray ionization tandem mass spectrometry (LC/MS/MS) analysis of short-chain fatty acids (SCFAs). The global cognition, specific cognitive domains (abstraction, orientation, attention, language, etc.) and severity of cognitive impairment, were evaluated by Montreal Cognitive Assessment (MoCA) scores. We further identified characteristic bacteria and SCFAs, and receiver operating characteristic (ROC) curve was used to determine the predictive value.ResultsOur results showed that the microbiota dysbiosis index was significantly higher in the severe and mild AD patients compared to the healthy control (HC). Linear discriminant analysis (LDA) showed that 12 families and 17 genera were identified as key microbiota among three groups. The abundance of Butyricicoccus was positively associated with abstraction, and the abundance of Lachnospiraceae_UCG-004 was positively associated with attention, language, orientation in AD patients. Moreover, the levels of isobutyric acid and isovaleric acid were both significantly negatively correlated with abstraction, and level of propanoic acid was significantly positively associated with the attention. In addition, ROC models based on the characteristic bacteria Lactobacillus, Butyricicoccus and Lachnospiraceae_UCG-004 could effectively distinguished between low and high orientation in AD patients (area under curve is 0.891), and Butyricicoccus and Agathobacter or the combination of SCFAs could distinguish abstraction in AD patients (area under curve is 0.797 and 0.839 respectively).ConclusionThese findings revealed the signatures gut bacteria and metabolite SCFAs of AD patients and demonstrated the correlations between theses characteristic bacteria and SCFAs and specific cognitive domains, highlighting their potential value in early detection, monitoring, and intervention strategies for AD patients.
Abnormal protein accumulations in the brain are linked to aging and the pathogenesis of dementia of various types, including Alzheimer’s disease. These accumulations can be reduced by cell indigenous mechanisms. Among these is autophagy, whereby proteins are transferred to lysosomes for degradation. Autophagic dysfunction hampers the elimination of pathogenic protein aggregations that contribute to cell death. We had observed that the adhesion molecule L1 interacts with microtubule-associated protein 1 light-chain 3 (LC3), which is needed for autophagy substrate selection. L1 increases cell survival in an LC3-dependent manner via its extracellular LC3 interacting region (LIR). L1 also interacts with Aβ and reduces the Aβ plaque load in an AD model mouse. Based on these results, we investigated whether L1 could contribute to autophagy of aggregated Aβ and its clearance. We here show that L1 interacts with autophagy-related protein 12 (ATG12) via its LIR domain, whereas interaction with ubiquitin-binding protein p62/SQSTM1 does not depend on LIR. Aβ, bound to L1, is carried to the autophagosome leading to Aβ elimination. Showing that the mitophagy-related L1-70 fragment is ubiquitinated, we expect that the p62/SQSTM1 pathway also contributes to Aβ elimination. We propose that enhancing L1 functions may contribute to therapy in humans.
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