Many neurodegenerative diseases are associated with the aggregation of misfolded 
proteins into amyloid oligomers or fibrils that are deposited as pathological 
lesions within areas of the brain. An attractive therapeutic strategy for 
preventing or ameliorating amyloid formation is to identify agents that inhibit 
the onset or propagation of protein aggregation. Here we demonstrate how 
solid-state nuclear magnetic resonance (ssNMR) may be used to identify key 
residues within amyloidogenic protein sequences that may be targeted to inhibit 
the aggregation of the host protein. For alpha-synuclein, the major protein 
component of Lewy bodies associated with Parkinson's disease, we have used a 
combination of ssNMR and biochemical data to identify the key region for 
self-aggregation of the protein as residues 77-82 (VAQKTV). We used our new 
structural information to design a peptide derived from residues 77 to 82 of 
alpha-synuclein with an N-methyl group at the C-terminal residue, which was able 
to disrupt the aggregation of alpha-synuclein. Thus, we have shown how 
structural data obtained from ssNMR can guide the design of modified peptides 
for use as amyloid inhibitors, as a primary step toward developing therapeutic 
compounds for prevention and/or treatment of amyloid diseases.