Aarushi Sharma, Kanchan Kashyap, Vivek Sharma*
Government College of Pharmacy, Rohru, Distt Shimla-171207, Himachal Pradesh, India
*Correspondence:
Dr. Vivek Sharma
Govt. College of Pharmacy, Rohru, Distt. Shimla-171207 Himachal Pradesh
Ph. No. +919816381966
Abstract
Parkinson's disease (PD) is one of the most common neurodegenerative syndrome manifested by rest tremors, rigidity, bradykinesia and postural instability. PD can also be associated with neurobehavioral complications (depression, anxiety), cognitive impairment (dementia) and autonomic dysfunction (orthostasis and hyperhidrosis). Typical neuropathological features of PD include degeneration of dopaminergic neurons located in the pars compacta of the substantia nigra that project to the striatum (nigro-striatal pathway) and depositions of cytoplasmic fibrillary inclusions (Lewy bodies) which contain ubiquitin and alpha-synuclein. Enormous progress has been made in the treatment of PD yet, Levodopa beside having complications like wearing off phenomenon, levodopa-induced dyskinesias (peak-dose dyskinesias, biphasic dyskinesias) and other motor complications remains the most potent drug for controlling PD symptoms. Catechol-o-methyl-transferase inhibitors, dopamine agonists and nondopaminergic therapy are other alternative modalities in the management of PD and may be used concomitantly with levodopa or one another. The neurosurgical treatment and stem cell therapy are other options but current clinical treatments for PD mainly focus on suppressing disease symptoms rather than restricting disease progression. Thus a quest to find a drug which not only cures complications but stops disease progression is yet to be met. In this line the c-Abl tyrosine kinase inhibitors has shown a great promise. cAbl participates in a variety of cellular functions, including regulation of the actin cytoskeleton, regulation of the cell cycle and the apoptotic/cell cycle arrest response to stress beside playing a crucial role in development of the central nervous system. Recent studies have shown c-Abl activation in Parkinson’s disease and suggests that therapies that block c-Abl could potentially change the course of the disease. These findings are especially timely because a c-Abl blocker called nilotinib has been proved successful in several animal models for PD.
Keywords: cAbl, Nilotinib, Oxidative stress, Parkin, Parkinson's disease
