Cell repair in Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder with the cardinal clinical features of muscular rigidity, resting tremor and bradykinesia. The prevalence of this disease is approximately 2% of those aged over 65 years, thus causing significant morbidity. The disease is characterized by degeneration of dopaminergic cells in the substantia nigra pars compacta, resulting in reduced dopaminergic input to the striatum. Significant clinical benefit can be achieved through the restoration of dopamine levels in this system with pharmacological interventions, although these therapies are only symptomatic and the disease progresses. Indeed, with disease progression other features often appear, including autonomic, affective and cognitive dysfunction, reflecting pathology at non-nigral sites. The occurrence of neural stem cells (NSCs) in the adult CNS, which, under certain conditions, are able to proliferate and renew neuronal numbers, has raised great expectations for alternative therapeutic applications in the treatment of PD. Indeed, it is potentially possible to harness this capacity either directly (increase of local proliferation, directed migration and differentiation) or indirectly (in vitro expansion before their transplantation), to facilitate the generation of specific cell types in order to replace missing neurons in neurodegenerative diseases. The manipulation of embryonic stem cells or their derivatives also offers a promising alternative as extensive proliferation may be achieved and, most importantly, directed differentiation to a dopaminergic phenotype is possible. Nevertheless, neuronal replacement will only be possible if proliferating or transplanted NSCs and their progeny can be harnessed at sites of pathology. It is the manipulation of stem cells both in vivo and in vitro, in the context of repairing the core pathological hallmark of PD, that is the main focus of this report.