Because copper homeostasis is deregulated in PD, it is of great significance to study the metal-binding site of wild-type α-syn (48-53, VVHGVA) and its pathological mutants (H50Q and G51D).
Using seed growth by monomer association (SeGMA) assays to measure fibril growth over 3 h in the presence of C2-α-syn monomer, we observed that some familial PD-associated α-syn mutations (<i>i.e.</i> H50Q and A53T) greatly increased growth rates, whereas others (E46K, A30P, and G51D) decreased growth rates.
The neuropathological features of these cases consistently share characteristics of PD and MSA and are distinct from PD patients carrying the H50Q or SNCA duplication.
Here, we describe a novel missense mutation in exon 4 of SNCA encoding a H50Q substitution in a patient with dopa-responsive Parkinson's disease with a family history of parkinsonism and dementia.
Understanding the aggregation mechanism of this H50Q mutant may help to establish the aggregation and phenotypic relationship of this novel mutant in PD.