TY - CHAP A1 - Michael F. Salvatore ED1 - Juliana Dushanova Y1 - 2012-02-08 PY - 2012 T1 - Targeting Tyrosine Hydroxylase to Improve Bradykinesia N2 - Parkinson's disease (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 cascade 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. BT - Mechanisms in Parkinson's Disease SP - Ch. 10 UR - https://doi.org/10.5772/16699 DO - 10.5772/16699 SN - PB - IntechOpen CY - Rijeka Y2 - 2020-08-06 ER -