Welcome to the

A database of biogenic peptides for inhibiting the aggregation of alpha-synuclein in humans by targeting toxic species. Learn more about it in our online manual.

Video tutorial

Citation

Pintado-Grima C, Bárcenas O, Iglesias V, Santos J, Manglano-Artuñedo Z, Pallarès I, Burdukiewicz M, Ventura S. aSynPEP-DB: a database of biogenic peptides for inhibiting α- synuclein aggregation, Database, 2023, https://doi.org/10.1093/database/baad084.

Contact

For comments and bugs please address Carlos Pintado-Grima.

For general questions about the research, please contact Salvador Ventura.

Acknowledgements

This work was funded by European Union’s Horizon 2020 research and innovation programme under GA 952334 (PhasAGE) and the Spanish Ministry of Science and Innovation (PID2019– 105017RB-I00).

Frequently asked questions (FAQs)

How are the peptides obtained?

The aSynPEP-DB considers four independent peptide source datasets: human neuropeptides, gut-microbiome peptides from healthy humans, human antimicrobial peptides and food-derived bioactive peptides. αSynPEP-DB rationalises that human peptides which prevent α-Synuclein (aSyn) pathogenic aggregation would likely be expressed in the nervous system. Besides, gut-microbiota is known to impact human physiology through the gut-brain axis [31460832]. Growing preclinical evidence shows gut aSyn can be transported to the brain via the vagus nerve [31255487] and that the interaction of aSyn by bacterial components [31460832], including extracellular peptides such as PSMα3 can modulate its aggregation [34145261]. Furthermore, we recently showed that the human anti-microbial peptide LL-37 selectively targeted aSyn toxic oligomers with nanomolar affinity [34145261]. Last but not least, some studies report that peptides incorporated from diet can be absorbed intact through the intestines [10394027]. Therefore, it is possible that some food-derive bioactive peptides could also target aSyn. Altogether, aSynPEP explores datasets of peptides that could be present in the human brain or gut, where of aSyn aggregation occurs in disease.

The mechanistic knowledge gained from the study of PSMα3, LL-37 and 5 rationally designed peptide variants allowed us to identify three physicochemical properties required for the high affinity and specific binding of the peptides to the pathogenic oligomeric species of aSyn: amphipathicyty, alpha-helical propensity and positive net charge [34145261]. This evidence motivated us to screen for peptide candidates displaying an optimal balance of these three structural/physicochemical properties in the three datasets of biogenic peptides, since they have the potential to inhibit aSyn aggregation by targeting the toxic species in this reaction (Figure 1).

Figure 1. The curation scheme shown above describes the bioinformatics pipeline developed starting with 5949 neuropeptides from NeuroPep [25931458], 6105 AMPs provided by DRAMP [34390348], 2747 gut-microbiome species and 6212 food-derived bioactive peptides from DFBP [35552640]. Gut-microbiome species from GMrepo were considered when their abundance was >= 5% in healthy humans [34788838]. Peptides were evaluated on heuristic rules reflecting the experimentally reported requirements for amphipathicity, alpha-helical propensity and net charge. Positive peptides were linked to external databases and enriched with therapeutic-relevant information. Finally, positive peptides from different datasets were merged into aSynPEP-DB, rendering a total of 123 peptides with potential to inhibit pathogenic aSyn aggregation.

Are the listed peptides experimentally validated?

Our previous research identified the key physicochemical properties peptides need to have for targeting aSyn toxic species and demonstrated that an adequate formulation of them allow to identify previously unreported active human peptides [34145261]. With this knowledge in hand, we developed αSynPEP-DB, a repository of biogenic peptides meeting such physicochemical requirements.

Except the already mentioned LL-37 (+ the non-endogenous PSMα3 and 5 synthetic peptides), the peptides listed in the database are not experimentally validated. We envision the aSynPEP-DB as a resource for researchers to identify and validate bioactive peptides that have the potential to inhibit aSyn aggregation thus building a new therapeutic/diagnostic paradigm in different synucleopathies. Additionally, identifying human endogenous molecules that interact with aSyn aggregates may define new targets or biomarkers to monitor in patients. The calculated structural/physicochemical properties of the peptides in this repository are all in the range of those shown to endorse the experimentally validated peptides with a high activity and specificity.

Is it possible to screen other peptides not considered by aSynPEP-DB?

αSynPEP-DB provides information on peptides from human proteins and healthy human microbacterial populations under the premise that they may function to avoid or reduce toxic aggregated species of aSyn in humans. To evaluate synthetic peptides or others not considered in the proposed pipeline, αSynPEP-DB provides a discriminative algorithm, which screens for peptides displaying a balance of the three experimentally validated physicochemical properties compatible with their high affinity interaction with aSyn toxic species. This algorithm can be accessed in the Algorithm tab.