Biochemistry of Parkinson's disease - insights from cellular models,TI Biochemistry of Parkinson's disease - insights from cellular models, animal models and human tissue specimens obtained by autopsy

摘要

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, characterized by tremor at rest, bradykinesia and rigidity as cardinal signs. Motor symptoms originate from the degeneration of dopaminergic neurones of the substantia nigra pars compacta, with a consequent loss of dopamine in the striatum and downstream functional alterations in the basal ganglia circuitry; non-motor symptoms of various types (autonomic impairment, gastrointestinal dysfunctions, cognitive defects, sleep disorders) frequently complete the clinical picture. Although PD is mostly a sporadic disorder, the contribution of genetic factors is being increasingly recognized; indeed, 15–30% of all PD cases are currently linked to a genetic background. Genetic causes of PD have allowed researchers to develop innovative cellular and animal models of PD pathogenesis and to look for speci?c alterations of biochemical pathways in PD patients carrying genetic mutations. Consequently, mechanisms arising from single protein modi?cations have been progressively linked together, so that we are now able to draw a quite extended map of how the different contributing factors to PD pathogenesis are interconnected.