The role of amphipathic and cationic helical peptides in Parkinson's disease

Abstract

Peptides are attracting a growing interest for therapeutic applications in biomedicine. In Parkinson's disease (PD), different human endogenous peptides have been associated with beneficial effects, including protein aggregation inhibition, reduced inflammation, or the protection of dopaminergic neurons. Such effects seem to be connected to the spatial arrangement of peptide side chains, and many of these human molecules share common conformational traits, displaying a distinctive amphipathic and cationic helical structure, which is believed to be crucial for their activities. This review delves into the relationship between these structural properties and the current evidence connecting biogenic peptides to the amelioration of PD symptoms. We discuss their implications in the disease, the different mechanisms of action, their state of validation, and their therapeutic potential.

Keywords: Parkinson's disease; peptides; structure; therapy; α‐synuclein.

FIGURE 1

Amphipathic and cationic human helical peptides with PD associations. For each peptide, both helical wheels and predicted 3D structures (ColabFold; Mirdita et al. 2022) are represented. Red colors indicate hydrophobic amino acids whereas dark and light blues indicate cationic and anionic residues, respectively. Prolines are colored in green and the remaining neutral residues in gray.

FIGURE 2

3D plot distribution of the predicted physicochemical properties for amphipathic and cationic helical peptides with previous evidences in alleviating PD symptoms.

FIGURE 3

Schematic representation of the main associated neuroprotective effects observed for amphipathic and cationic helical peptides in PD. Figure created with resources of Flaticon.com.