ABSTRACT
The pathogenesis of Parkinson’s disease remains unknown, even 186 yr after its first description. However, major advances in molecular genetics in the past few decades have revolutionized the classification of Parkinson’s disease and Parkinson-plus syndromes. A strong genetic basis has been established for early-onset Parkinson’s disease, and genetic factors have been identified that play a crucial role in a subset of patients with the lateonset, sporadic form. Several genetically, clinically, and pathologically distinct forms of these disorders can be caused by mutations in α-synuclein, parkin, UCH-L1, DJ1, NR4A2, ND4, tau, or as yet unknown causative genes. Molecular characterization has also provided clues regarding their pathogenesis, leading to the categorization of these disorders into polyglutamine disorders, synucleinopathies, and tauopathies. This chapter reviews the current knowledge of the genetic basis of heredofamilial parkinsonism. With growing interest in this field, additional genes and susceptibility loci will undoubtedly continue to be discovered.
