Synucleinopathies in neurodegenerative diseases: Accomplices, an inside job and selective vulnerability

Abstract Pathogenesis of degenerative diseases is complex and multifaceted. The disease phenotypes depend on the location of injury/damage in the brain networks and pathologically are characterized by loss of brain cells. The reason for this loss appears to be an accumulation of misfolded and dysfunctional proteins that trigger apoptotic cell death. The role of alpha-synuclein mutations, its interaction with other proteins and the cellular environment is discussed in the context of selective neuron loss.