Amyloidogenic proteins amyloid-beta peptide (A beta) and alpha-synuclein (alpha-syn) self-assemble into fibrillar amyloid deposits, senile plaques and Lewy bodies, pathological features of Alzheimer's and Parkinson's diseases, respectively. Interestingly, a portion of Alzheimer's disease cases also exhibit aggregation of alpha-syn into Lewy bodies, and growing evidence also suggests that A beta and alpha-syn oligomers are toxic. Therefore, the simultaneous inhibition through sequestration of the two amyloidogenic proteins may constitute a promising therapeutic strategy. Recently discovered beta-wrapin proteins pave the way toward this direction as they can inhibit the aggregation and toxicity of both A beta and alpha-syn. Here, we used computational methods, primarily molecular dynamics simulations and free energy calculations, to shed light into the key interaction-based commonalities leading to the dual binding properties of beta-wrapins for both amyloidogenic proteins, to identify which interactions potentially act as switches diminishing beta-wrapins binding activity for A beta/alpha-syn, and to examine the binding properties of the current most potent beta-wrapin for A beta. Our analysis provides insights into the distinct role of the key determinants leading to)beta-wrapin binding to AP and alpha-syn, and suggests that the A beta (18)VFFAED(23) and alpha-syn (38)LYVGSK(43) are key domains determining the binding specificity of a beta-wrapin. Our findings can potentially lead to the discovery of novel therapeutics for Alzheimer's and Parkinson's diseases.