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The Vekrellis Lab is investigating mechanisms involved in the pathogenesis of neurodegenerative disorders. Many neurodegenerative diseases, including prion disease, Alzhmeimer's and Parkinson's Disease are characterized by the accumulation of proteins with specific conformational states harboring beta sheet-rich secondary structures. These result in oligomeric species and plaque and tangle formation or formation of intracellular fibrillar aggregates. Such aberrant conformations appear to be toxic to neurons and to lead to death in the adult nervous sytem, but exactly which species are involved is unclear. Although speculated, a direct effect between α-synuclein oligomers and neuronal dysfunction has not yet been demonstrated. Furthermore, the mechanisms through which intracellular soluble oligomers exert their aberrant effects on neurons are largely unknown.