Parkinson's disease (PD) is progressive neurodegenerative disorder. A combination of medical and surgical treatments has improved the quality of the lives of most PD patients. But the relentless progression of degeneration of the substantial nigra and consequent loss of dopamine in the basal ganglia ultimately leads to a severe debilitating state. Efforts to slow the disease even to a small degree will extend the life span and improve the quality of a patient's life and reduce the national burden of cost of care of PD patients.At present there are no drugs that can slow the progression of the disease. In this proposal it is hypothesized, that among all the available compounds, nicotine shows significant promise to be a neuroprotective agent for the degenerating dopaminergic neurons in PD. We will discuss evidence to support that: 1. Nicotine is neuroprotective in several models of neurotoxicity, 2. The neuroprotective effects of nicotine are mediated via several well established cell survival and anti-apoptotic molecular cascades, 3. The degenerating dopaminergic neurons in PD do show evidence of apoptotic death, 4. Nicotine is neuroprotective in animal models of PD, and 5. Nicotine's neuroprotective actions are accomplished by the activation of P13K/Akt antiapoptotic pathways by alpha4 - beta2 and aIpha7 - beta2 nicotinic receptors, which are abundant in the substantial nigra and striatum. A tentative research plan to conduct clinical trial using Transdermal nicotine patches is also proposed.
| Wills, Anne-Marie A; Elm, Jordan J; Ye, Rong et al. (2016) Cognitive function in 1736 participants in NINDS Exploratory Trials in PD Long-term Study-1. Parkinsonism Relat Disord 33:127-133 |
| Wills, Anne-Marie A; Pérez, Adriana; Wang, Jue et al. (2016) Association Between Change in Body Mass Index, Unified Parkinson's Disease Rating Scale Scores, and Survival Among Persons With Parkinson Disease: Secondary Analysis of Longitudinal Data From NINDS Exploratory Trials in Parkinson Disease Long-term Study 1 JAMA Neurol 73:321-8 |
| Elm, Jordan J; NINDS NET-PD Investigators (2012) Design innovations and baseline findings in a long-term Parkinson's trial: the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease Long-Term Study-1. Mov Disord 27:1513-21 |
