Abstract
Parkinson’s disease (PD) is a slowly progressive, age-related, second most common neurodegenerative disorder after Alzheimer’s disease of unknown etiology. Dopamine replacement therapies were introduced five decades ago and still remain the mainstay of treatment for Parkinson’s disease. However, with long-term treatment with L-dopa, more than 50% of patients were found to develop motor response complications approximately after 4 - 5 years of initiation of continuous treatment, in 80% of patients treated for 10 years, and in nearly 100% patients with young-onset disease. The complications of long–term treatment with levodopa include-motor fluctuations, dyskinesias, and nonmotor fluctuations are such as mood disturbance, cognitive dysfunction, dysautonomia and pain. Till date, there are various therapeutic approaches having been developed for the treatment of advanced PD comprising Pharmacotherapy, neurotrophic factors, surgical procedures such as DBS, cell-based therapies and gene therapies. The pharmacological and surgical therapies are only aiming to improve the symptoms of PD, but none are proven to have a significant effect on the underlying disease process with respect to either slowing disease progression or restoring the affected dopaminergic neurons. Although there is no cure for PD, Gene based therapy has significant prospective advantages over the conventional treatment modalities for PD, as it could theoretically be used to preserve or restore dopaminergic neurons affected by PD through the action of neurotrophic factors or alternatively increase the availability of enzymes required for dopamine synthesis. All commonly employed PD therapies focus on the amelioration of symptoms and do not cure disease. In this review only we summarize the newer therapeutic strategies for the treatment of PD such as anti-inflammatories, neurotrophic factors, neurosurgical procedures (DBS), cell based therapies and gene therapies.
Highlights
Parkinson’s disease (PD) is a slowly progressive, age-related, second most common neurodegenerative disorder worldwide, after Alzheimer’s disease (AD) of unknown etiology [1]-[4]
The study showed that when PC12 cells were pretreated with luteolin (20 μM) 30 min prior to 6-OHDA (100 μM) exposure, 6-OHDA-induced ROS overproduction, cytotoxicity, caspase-3 activation, mRNA expression of BIM, TRB3 and GADD34 were significantly attenuated leading to decreases in phospho-eIF2α, ATF4, GRP78 and CHOP and these results have suggested that diminishing intracellular ROS formation and down-regulation of p53, UPR and Nrf2-ARE pathways and it may be involved in the neuroprotective effect of luteolin [42]
An open label, phase I trial study was evaluated with administration of a unilateral injection of AAV-glutamic acid decarboxylase (GAD) into the subthalamic nucleus of patients with Parkinson’s disease with low-dose, four medium-dose, and four high-dose AAV-GAD at New York Presbyterian Hospital and the study was identified that there were no adverse events related to gene therapy and there was significant improvement in motor Unified Parkinson’s Disease Rating Scale (UPDRS) scores (p = 0.0015), predominantly on the side of the body that was contralateral to surgery, were seen 3 months after gene therapy and persisted up to 12 months
Summary
Parkinson’s disease (PD) is a slowly progressive, age-related, second most common neurodegenerative disorder worldwide, after Alzheimer’s disease (AD) of unknown etiology [1]-[4]. Environmental factors, including age, sex, blood urate levels, NSAID use, head trauma, anxiety disorders, exposure to lead, manganese, iron, copper, solvents and pesticides (e.g. rotenone, paraquat, maneb, dieldrin, pyrethroids, organophosphates and Combined ambient exposure to ziram and paraquat) may be an important risk factor for PD which induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillization and neuronal cell loss [10][14]. The motor symptoms of PD include four cardinal features: bradykinesia, rest tremor, rigidity, postural instability and gait impairment. 1. Bradykinesia: refers to slowness of movements with a progressive loss of amplitude or speed during attempted rapid alternating movements of body segments. Rigidity: refers to an increased muscle tone felt during examination by passive movement of the affected segment (limbs or neck), involving both flexor and extensor muscle groups
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
