The misfolding and progressive aggregation of specific
proteins in selective regions of the nervous system is a seminal occurrence in many
neurodegenerative disorders, and the interaction between pathological/toxic
proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic and experimental differences, increasing evidence indicates considerable overlap between
synucleinopathies,
tauopathies and other
protein-misfolding diseases. Inclusions, often characteristic hallmarks of these disorders, suggest interactions of pathological
proteins enganging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic
proteins in the pathogenesis of Alzheimer, Parkinson, Huntington and
prion diseases, have confirmed correlations/overlaps between these and other
neurodegenerative disorders. Emerging evidence, in addition to synergistic effects of
tau protein,
amyloid-β, α-
synuclein and other pathologic
proteins, suggests that
prion-like induction and spreading, involving secreted
proteins, are major pathogenic mechanisms in various
neurodegenerative diseases, depending on genetic backgrounds and environmental factors. The elucidation of the basic molecular mechanisms underlying the interaction and spreading of pathogenic
proteins, suggesting a dualism or triad of neurodegeneration in
protein-misfolding disorders, is a major challenge for modern neuroscience, to provide a deeper insight into their pathogenesis as a basis of effective diagnosis and treatment.