Fig. 1

αS aggregation into Lewy bodies in PD and regions of interest. Top: In PD, alpha-synuclein (αS) is able to aggregate, via oligomers, into protofibrils, fibrils and Lewy bodies, leading to the death of dopaminergic neurons in the substantia nigra pars compacta region of the brain, which ultimately results in PD symptoms. Also shown is an aggregation profile in which the lag-phase, exponential phase and stationary phases are shown along with corresponding species of αS known to form. Figure created with BioRender.com. Bottom: the primary structure of αS is shown divided into three distinct regions. (1) Amphipathic N-terminal region (residues 1–60) containing seven imperfect repeats of the KTKEGV sequence and where most familial mutations linked to early-onset PD are found [62]. (2) NAC (non-amyloid component) domain, a central hydrophobic region (residues 61–95) involved in protein aggregation. (3) A negatively charged and proline-rich C-terminal region (residues 96–140). Point-mutations linked to early onset-PD (A30P/G, E46K, H50Q, G51D, A53T/E/V respectively) are shown in red for reference. Also shown are peptide sequence identifiers (green) corresponding to compounds in Table 1 and where within αS, and/or the aggregation pathway, that they are thought to target and impact