Diagnostics, rehabilitation and models of Parkinson’s disease

Abstract

Diagnostics and rehabilitation of Parkinson’s disease (PD) presents the current information pertaining to etiology, early biomarkers for diagnostics, novel methods to evaluate symptoms, multidisciplinary rehabilitation, new applications of brain imaging and invasive methods to the study of PD. Researchers have only recently begun to focus on the non-motor symptoms of PD, which are poorly recognized and inadequately treated by clinicians. The non-motor symptoms of PD have a significant impact on patient quality of life and mortality, and include cognitive impairments, autonomic, gastrointestinal, and sensory symptoms. Indepth discussion of the use of imaging tools to study disease mechanisms is also provided, with emphasis on the abnormal network organization in parkinsonism. Deep brain stimulation management is a paradigm-shifting therapy for PD, essential tremor and dystonia. In the recent years, new approaches of early diagnostics, training programmes and treatments have vastly improved the lives of people with PD, substantially reducing symptoms and significantly delaying disability. PD results primarily from the death of dopaminergic neurons in the substantia nigra. Current PD medications treat symptoms; none halt or retard dopaminergic neuron degeneration. The main obstacle to developing neuroprotective therapies is a limited understanding of the key molecular mechanisms that provoke neurodegeneration. The discovery of PD genes has led to the hypothesis that misfolding of proteins and dysfunction of the ubiquitin-proteasome pathway are pivotal to PD pathogenesis. Previously implicated culprits in PD neurodegeneration, mitochondrial dysfunction and oxidative stress, may also act in part by causing the accumulation of misfolded proteins, in addition to producing other deleterious events in dopaminergic neurons. Neurotoxin-based models have been important in elucidating the molecular cas-cade of cell death in dopaminergic neurons. PD models based on the manipulation of PD genes should prove valuable in elucidating important aspects of the disease, such as selective vulnerability of substantia nigra dopaminergic neurons to the degenerative process.