Dissecting Alzheimer's Disease Molecular Substrates by Proteomics and Discovery of Novel Post-translational Modifications

Deolankar, Sayali Chandrashekhar; Patil, Arun H.; Koyangana, Shashanka G; Subbannayya, Yashwanth; Prasad, T. S. Keshava; Modi, Prashant Kumar

doi:10.1089/omi.2019.0085

Cited by 13 publications

(13 citation statements)

References 60 publications

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“…Regarding the network analysis of AMPs altered in AD, our data give further evidence for the importance of inflammation and innate defense mechanisms in the development of the disease. Beside these general functions, alterations affecting protein post-translational modification, which might be related to hyperphosphorylation of tau (or of other proteins) ( Tan et al, 2015 ), ubiquitination ( Measho et al, 2018 ), glycosylation ( Wang et al, 2017 ), or citrullination ( Deolankar et al, 2019 ) of brain proteins characteristic of AD could be demonstrated. The dietary excess and impairment of lipid metabolism, along with insulin intolerance and the lack of neurotrophic factors, can lead to the cognitive decline characteristic of AD ( Schindowski et al, 2008 ; de la Monte, 2009 ; Allen et al, 2011 ; Hu et al, 2013 ; Dharshini et al, 2019 ; Mitra et al, 2019 ; Kellar and Craft, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Construction of Unified Human Antimicrobial and Immunomodulatory Peptide Database and Examination of Antimicrobial and Immunomodulatory Peptides in Alzheimer’s Disease Using Network Analysis of Proteomics Datasets

et al. 2021

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The reanalysis of genomics and proteomics datasets by bioinformatics approaches is an appealing way to examine large amounts of reliable data. This can be especially true in cases such as Alzheimer’s disease, where the access to biological samples, along with well-defined patient information can be challenging. Considering the inflammatory part of Alzheimer’s disease, our aim was to examine the presence of antimicrobial and immunomodulatory peptides in human proteomic datasets deposited in the publicly available proteomics database ProteomeXchange (http://www.proteomexchange.org/). First, a unified, comprehensive human antimicrobial and immunomodulatory peptide database, containing all known human antimicrobial and immunomodulatory peptides was constructed and used along with the datasets containing high-quality proteomics data originating from the examination of Alzheimer’s disease and control groups. A throughout network analysis was carried out, and the enriched GO functions were examined. Less than 1% of all identified proteins in the brain were antimicrobial and immunomodulatory peptides, but the alterations characteristic of Alzheimer’s disease could be recapitulated with their analysis. Our data emphasize the key role of the innate immune system and blood clotting in the development of Alzheimer’s disease. The central role of antimicrobial and immunomodulatory peptides suggests their utilization as potential targets for mechanistic studies and future therapies.

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Section: Discussionmentioning

confidence: 99%

Construction of Unified Human Antimicrobial and Immunomodulatory Peptide Database and Examination of Antimicrobial and Immunomodulatory Peptides in Alzheimer’s Disease Using Network Analysis of Proteomics Datasets

et al. 2021

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“…N-terminal signal peptides for proteins were mapped using SignalP version 5.0 () . Label-free quantification of identified proteins was carried out by using an in-house intensity-based absolute quantification (iBAQ) tool …”

Section: Materials and Methodsmentioning

confidence: 99%

“…16 Label-free quantification of identified proteins was carried out by using an in-house intensity-based absolute quantification (iBAQ) tool. 17…”

Section: Bioinformatics and Functional Analysismentioning

confidence: 99%

Deep Proteome Profiling of Semen of Indian Indigenous Malnad Gidda (Bos indicus) Cattle

et al. 2020

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Malnad Gidda is a dwarf indigenous cattle breed of India, which is known for its uniqueness of calving every year under a low input grazing system of rearing. Bulls of Malnad Gidda are known to be highly fertile even in stress conditions. However, the proteomic profiling of semen of this breed has not been investigated so far, which might provide a platform for a better understanding of its semen quality and male fertility. Therefore, we made an effort to characterize and quantify the proteome of seminal plasma and spermatozoa components of Malnad Gidda semen using a high-resolution mass spectrometry platform. We identified 2814 proteins from spermatozoa and 1974 proteins from the seminal plasma of this breed. Furthermore, >90% of proteins from each fraction were quantified using the intensity-based absolute quantification. We observed signal peptides in 33% of seminal plasma proteins, indicating their secretory nature. Gene Ontology analysis revealed their involvement in cytoskeletal assembly associated with sperm head, sperm motility, acrosome reaction, seminal plasma binding, and spermatogenesis-associated protein. An in-depth proteome profiling of semen of a unique indigenous cattle breed of India was carried out. Our findings could provide a reference for further studies on sperm functions, semen quality, and reproductive health of Bos indicus cattle. Mass spectrometry data generated in this study is deposited and publicly made available through ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD014172.

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“…GSAP significantly and selectively elevates the Aβ production without altering γsecretase normal functions such as notch cleavage [49][50][51]. γsecretase cleaves the C83 and C99 resulting in the production of fragments such as P3, varied length of Aβ (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49), and APP intracellular domain (AICD) [42]. C89 processing by γsecretase reveals generation of truncated Aβ11-40/42 (Aβ') peptides [52].…”

Section: App-secretases Processing and Aβ Generationmentioning

confidence: 99%

“…The sulfation occurs at Tyr217 and Tyr262 residues of APP, however the exact sulfation sites and functions are not completely discovered [ 37 ]. On the other hand, the PTMs analysis of AD molecules revealed citrullination (Arg301), phosphorylation (Ser366, Ser441), and methylation (Lys624, Lys699) of APP protein [ 38 ]. In addition, citrullination (Arg5→Cit) and deamidation (Asn27→Asp) of Aβ fragments affects the fibrillation rate of Aβ [ 39 ].…”

Section: App Processingmentioning

confidence: 99%

Alzheimer’s Disease: A Molecular View of β-Amyloid Induced Morbific Events

et al. 2021

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Amyloid-β (Aβ) is a dynamic peptide of Alzheimer’s disease (AD) which accelerates the disease progression. At the cell membrane and cell compartments, the amyloid precursor protein (APP) undergoes amyloidogenic cleavage by β- and γ-secretases and engenders the Aβ. In addition, externally produced Aβ gets inside the cells by receptors mediated internalization. An elevated amount of Aβ yields spontaneous aggregation which causes organelles impairment. Aβ stimulates the hyperphosphorylation of tau protein via acceleration by several kinases. Aβ travels to the mitochondria and interacts with its functional complexes, which impairs the mitochondrial function leading to the activation of apoptotic signaling cascade. Aβ disrupts the Ca2+ and protein homeostasis of the endoplasmic reticulum (ER) and Golgi complex (GC) that promotes the organelle stress and inhibits its stress recovery machinery such as unfolded protein response (UPR) and ER-associated degradation (ERAD). At lysosome, Aβ precedes autophagy dysfunction upon interacting with autophagy molecules. Interestingly, Aβ act as a transcription regulator as well as inhibits telomerase activity. Both Aβ and p-tau interaction with neuronal and glial receptors elevate the inflammatory molecules and persuade inflammation. Here, we have expounded the Aβ mediated events in the cells and its cosmopolitan role on neurodegeneration, and the current clinical status of anti-amyloid therapy.

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Dissecting Alzheimer's Disease Molecular Substrates by Proteomics and Discovery of Novel Post-translational Modifications

Cited by 13 publications

References 60 publications

Construction of Unified Human Antimicrobial and Immunomodulatory Peptide Database and Examination of Antimicrobial and Immunomodulatory Peptides in Alzheimer’s Disease Using Network Analysis of Proteomics Datasets

Construction of Unified Human Antimicrobial and Immunomodulatory Peptide Database and Examination of Antimicrobial and Immunomodulatory Peptides in Alzheimer’s Disease Using Network Analysis of Proteomics Datasets

Deep Proteome Profiling of Semen of Indian Indigenous Malnad Gidda (Bos indicus) Cattle

Alzheimer’s Disease: A Molecular View of β-Amyloid Induced Morbific Events

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