Systematic analysis of diabetes- and glucose metabolism-related proteins and its application to Alzheimer’s disease

Abstract

Alzheimer disease has been defined as Type 3 Diabetes due to their shared metabolic profiles. Like our previously research, results of Alzheimer's disease and other neurodegenerative diseases, systematic analysis of diabetes-and glucose metabolism-related proteins also provides help in the treatment of Alzheimer's patients. Some interesting results indicate that diabetes-related proteins (DRPs) are rich in Lys and the content of Trp can distinguish between type 1 and type 2 diabetes mellitus in particular, while glucose metabolism-related proteins (GMRPs) possess Leurich and Trp-poor character. Moreover, the usage biases of codons depend on GC contents to a great extent, in concord with all codons of the highly expressed genes with the terminal of C/G. Especially, the deficit of CpG dinucleotides is largely attributed to the hypermutability of methylated CpGs to UpGs by the mutational pressure. Besides a common node insulin receptor, there are some similar node proteins, such as glucose transporter member, protein tyrosine phosphatase, and adipose metabolism signal protein. The sharing proteins involve glucagon, amylin, insulin, PPARγ, angiopoietin, PC-1/ENPP1, and adiponectin mediated signal pathway. Meanwhile, the gene sequences of node proteins contained the binding sites of 37 transcription factors divide into four kinds of superclasses. Additionally, BAD complex can integrate pathways of glucose metabolism and apoptosis by BH3 domain of BAD directly interacting with GK as well as GK binding with the consensus motif [G]-[1]-[K]-[2]-[S/T] or [L/M]-[R/K]-[2]-[T] of PP1 orWAVE1. This facilitates the therapies for diabetes mellitus as well as Alzheimer's disease. Science and Engineering 6 (2013) 615-644 616 portions, because of an increased number of elderly people, and a greater prevalence of obesity and sedentary lifestyles [8,9]. Diabetes mellitus is associated with decreased body insulin production than required (type 1) and impaired insulin signaling (type 2/T2DM). Diabetes especially T2DM and AD follow the same pathological mechanisms resulting in misfolded proteins, insulin impairment, abnormal glucose metabolism, abnormal fatty acid metabolism, mitochondrial dysfunction, and high oxidative stress [1]. These shared metabolic profiles and diabetes as extreme risk factor for AD lead to the assumption that AD may reflect type-3 diabetes.We have previously finished construction of cell model for screening Alzheimer's drugs [10], codon usage biases in AD and other neurodegenerative diseases [11], and protein-protein interactions related to AD based on complex network [12]. Similarly, we are to propose a computational analysis on codon biases of some proteins related to diabetes and glucose metabolism, hoping that the findings might be useful for developing new therapeutic treatment for diabetes as well as AD. Moreover, the proteins related to diabetes are located at signal transduction pathway [13,14], gene control pathway [15,16], glucose metabolic pathway [17,18], etc. A large number of research work on t...

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A structured brain‐wide and genome‐wide association study using ADNI PET images

“…Our findings also provided evidence about indirect genetic effects on certain chemical compounds or protein translocation, which are reflected in the PET scans and may be associated with AD. For example, Dai et al (2013) and Sakamoto & Holman (2008) demonstrated that TBC1D4 plays a role in regulation of GluT4 traffic, which, on the other hand is associated with AD (Talbot et al, 2012;Yang, Li, & Liu, 2013). Nolte et al (2006) and Lu, He, & Zhong (2007) have given a chain of relationships of HOXD4 gene to PAX6 protein to AD.…”