Role of Autophagy in Parkinson’s Disease

Parkinson’s disease (PD) is a prevalent neurodegenerative movement disorder whose occurrence crosses geographic, racial and social boundaries affecting 1-2% of the population above the age of 65 (Dorsey et al., 2007). Clinically, the disease is attended by a constellation of motoric deficits that progressively worsen with age, which ultimately leads to near total immobility. Although pathological changes are distributed in the PD brain (Braak et al., 2003), the principal lesion that underlies the characteristic motor phenotype of PD patients is unequivocally the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the midbrain. This neuronal loss results in a severe depletion of striatal dopamine (DA) and thereby an impaired nigrostriatal system that otherwise allows an individual to execute proper, coordinated movements. Accordingly, pharmacological replacement of brain DA via L-DOPA administration represents an effective symptomatic recourse for the patient (espe‐ cially during the initial stages of the disease) and remains a clinical gold standard treatment for PD. However, neither L-DOPA nor any currently available therapies could slow or stop the insidious degenerative process in the PD brain. Thus, PD remains an incurable disease. Invariably, the debilitating nature and morbidity of the disease present significant healthcare, social, emotional and economic problems. As the world population rapidly ages, these problems undoubtedly would also increase. According to a recent report, more than 4 million individuals in Europe’s five most and the world’s ten most populous countries are currently afflicted with PD (Dorsey et al., 2007). In less than 20 years’ time, the number of PD sufferers is projected to increase to close to 10 million (i.e. in 2030). This is definitely a worrying trend, and one that aptly emphasizes the urgency to develop more effective treatment modalities for the PD patient. Towards this endeavour, a better understanding of the molecular mechanism(s) that underlies the pathogenesis of PD would definitely be helpful, as the illumination of which