Abstract
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.
Highlights
Antimicrobial and immunomodulatory peptides (AMPs) are produced by most of the organisms including animals and a variety of other species like bacteria, fungi, etc. (Epand and Vogel, 1999; Zhe and Guangshun, 2004)
As far as AMPs have a role in innate immune response, which is involved in the pathophysiology of Alzheimer’s disease (AD), and some AMPs were directly linked to AD, our aim was to examine in which extent the AMPs might be implicated in the pathogenesis of this neurodegenerative disease
All human AMPs listed in the Collection of Anti-Microbial Peptides (CAMP) (Thomas et al, 2009), Antimicrobial Peptide Database (APD) (Zhe and Guangshun, 2004), Database of Antimicrobial Peptides (Jhong et al, 2019), Linking Antimicrobial Peptides (LAMP) (Zhao et al, 2013), and Database of Antimicrobial Activity and Structure of Peptides (DBAASP) (Gogoladze et al, 2014) online databases were retrieved
Summary
Antimicrobial and immunomodulatory peptides (AMPs) are produced by most of the organisms including animals and a variety of other species like bacteria, fungi, etc. (Epand and Vogel, 1999; Zhe and Guangshun, 2004). Human AMPs are elements of the innate immune system (Prashant et al, 2018) and constitute a first line of defense protecting the host from invading pathogens (Epand and Vogel, 1999; Zhe and Guangshun, 2004) They can be gene-coded peptides or small proteins, which are either constitutively expressed such as LL-37 cathelicidin, human beta defensin 1 (HBD1), dermcidin (DCD) (Bardan et al, 2004; Brandwein et al, 2017) or induced like HBD2, HBD3, and RNAse (Bardan et al, 2004; Brandwein et al, 2017) to fight off pathogens (Prashant et al, 2018; Jhong et al, 2019). AMPs have a role in apoptosis, phagocytosis, wound healing, fertilization, etc. (Jenssen et al, 2006; Prashant et al, 2018)
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