Neurodegenerative signaling factors and mechanisms in Parkinson's pathology

Parkinson's disease (PD) is a chronic and progressive degenerative disorder of central nervous system which is mainly characterized by selective loss of dopaminergic neurons in the nigrostrial pathway. Clinical symptoms of this devastating disease comprise motor impairments such as resting tremor, bradykinesia, postural instability and rigidity. Current medications only provide symptomatic relief but fail to halt the dopaminergic neuronal death. While the etiology of dopaminergic neuronal death is not fully understood, combination of various molecular mechanisms seems to play a critical role. Studies from experimental animal models have provided crucial insights into the molecular mechanisms in disease pathogenesis and recognized possible targets for therapeutic interventions. Recent findings implicate the involvement of abnormal protein accumulation and phosphorylation, mitochondrial dysfunction, oxidative damage and deregulated kinase signaling as key molecular mechanisms affecting the normal function as well survival of dopaminergic neurons. Here we discuss the relevant findings on the PD pathology related mechanisms and recognition of the cell survival mechanisms which could be used as targets for neuroprotective strategies in preventing this devastating disorder.