Journal
MOVEMENT DISORDERS
Volume 27, Issue 1, Pages 8-30Publisher
WILEY
DOI: 10.1002/mds.23795
Keywords
Parkinson's disease; neuropathologic criteria; alpha-synuclein; Lewy pathology; morphologic staging; clinical relevance; heterogeneity of subtypes; relation of alpha-synuclein with other proteins
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Funding
- Society for Support of Research in Experimental Neurology, Vienna, Austria
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Parkinson's disease (PD), one of the most frequent neurodegenerative disorders, is no longer considered a complex motor disorder characterized by extrapyramidal symptoms, but a progressive multisystem or-more correctly-multiorgan disease with variegated neurological and nonmotor deficiencies. It is morphologically featured not only by the degeneration of the dopaminergic nigrostriatal system, responsible for the core motor deficits, but by multifocal involvement of the central, peripheral and autonomic nervous system and other organs associated with widespread occurrence of Lewy bodies and dystrophic Lewy neurites. This results from deposition of abnormal alpha-synuclein (alpha Syn), the major protein marker of PD, and other synucleinopathies. Recent research has improved both the clinical and neuropathological diagnostic criteria of PD; it has further provided insights into the development and staging of alpha Syn and Lewy pathologies and has been useful in understanding the pathogenesis of PD. However, many challenges remain, for example, the role of Lewy bodies and the neurobiology of axons in the course of neurodegeneration, the relation between alpha Syn, Lewy pathology, and clinical deficits, as well as the interaction between alpha Syn and other pathologic proteins. Although genetic and experimental models have contributed to exploring the causes, pathomechanisms, and treatment options of PD, there is still a lack of an optimal animal model, and the etiology of this devastating disease is far from being elucidated. (C) 2011 Movement Disorder Society
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