Silke Nuber and coworkers generated and deeply characterized numerous transgenic rodent models to study PD and related disorders, including the first inducible α-synuclein (αS) transgenic mice, humanized BAC-wildtype human αS tg rat models. They also analyzed impact of interaction partners (i.e., calpain, synphilin) in double-mutant mice as well as of PD-neurotoxins (MPTP, paraquat) in cell culture and in vivo. Nuber now focuses her research on unique mice based on mutations that promote αS tetramer-abrogation (i.e., 3K αS tg mice). The mice develop robust motor phenotypes, including tremor and L-DOPA responsive gait abnormalities and brain neuropathologies resembling PD down to the ultrastructural level. She and her colleagues published the finding of PD models in over 30 peer-reviewed articles.
The Nuber Laboratory is part of the Ann Romney Center for Neurologic Diseases (ARCND) at Brigham and Women’s Hospital, Harvard Medical School. The laboratory is set to understand mechanisms by which αS produces PD, using a wide range of methods, including protein biochemistry, immunohistochemistry, light, confocal and electron microscopy and motor and cognitive animal behavior analyses.