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Minerva Psichiatrica 2009 March;50(1):1-26


language: English

Neuropathology and neurochemistry of Parkinson’s disease: the never-ending story or the story with no beginning?

Uversky V. N. 1, 2

1 Institute for Intrinsically Disordered Protein Research Center for Computational Biology and Bioinformatics Department of Biochemistry and Molecular Biology Indiana University School of Medicine, Indianapolis, IN, USA 2 Institute for Biological Instrumentation Russian Academy of Sciences, Pushchino Moscow Region, Russia


Parkinson’s disease (PD) is a slowly progressive disorder that primarily affects substantia nigra, where the gradual degeneration of the dopaminergic neurons takes place, causing a reduction in the dopamine content and producing a set of characteristic symptoms. Some surviving neurons contain pathological hallmarks of PD, proteinaceous inclusions known as Lewy bodies (LBs) and Lewy neurites (LNs). Being almost two centuries old, the field of PD has experienced an explosive development during the last three decades. As a result, significant progress has been achieved in understanding this disease. The classic view of PD as a disorder with highly localized neurodegeneration and accumulation of characteristic inclusions, seemingly causing cell death, has been changed. Our studies in PD neuropathology have moved us away from the focused consideration of this disease as being solely a motor deficit malady. Our research in PD neurochemistry has brought us far beyond the naïve mechanical consideration of the localized neurodegeneration and accumulation of LBs and LNs in substantia nigra. Now, PD is recognized as a multifactorial disease in a broad essence of this word. It clearly affects the body on multiple levels, hits different systems, produces various symptoms, and generates diverse biochemical outputs. PD is a disease with a multicatorial etiology, where any of a broad set of intrinsic and extrinsic factors (protein misfolding and aggregation, mutations, genetic predisposition, oxidative damage, impairement of the quality control system, gliosis, environmental toxins, mitochondiapathy, etc.), or their various combinations, can trigger the development of pathology. This review represents a set of rather subjective snapshots of some recent developments in various sub-areas of this field. Its major goals are to show the highly dynamic nature of research and to emphasize that the current status of the field can be described by two words: “still looking”.

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