Neuroprotective Agents for Management of Parkinson’s disease
Year: 2015
Type: article
Abstract: Introduction Parkinson disease (PD), the second most common neurodegenerative disorder after Alzheimer’s disease, is a movement disorder manifested by bradykinesia, rest tremor, postural instability and rigidity. It is an idiopathic, chronic and progressive syndrome that affects both physical and mental functions (13). As for the etiology of the disease, most cases are of unknown origin (idiopathic PD). Genetic, environmental factors (e.g. toxin exposure) and age related changes play a significant role in the pathogenesis of PD. In addition, free radical production causes oxidative and nitrosative stress which is linked to inflammation and leads to cell death and neuro-degeneration (1, 2, 4, 5). Figure 1 shows how neuroinflammation and oxidative stress can damage dopaminergic neurons in patients who suffer from PD (6). In vivo and In vitro studies show that neuroinflammation has a role in PD and serum levels of interleukin 2, Tumor Necrosis Factor (TNF) α, interleukin6, nitric oxide and others are increased in these patients. Also antibodies against oxidized dopamine have been found in the sera of above patients. In addition, some oxidative factors like interleukin 6 and 1β, TNFα, osteopontin are present in cerebrospinal fluid of patients with PD. Epidemiologic studies show that individuals who take non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) have a lower risk of developing PD. This risk is also low in people who take two or more tablets of aspirin (6). Neuroprotection should be considered for prevention of further loss of neurons in substantia nigra especially for patients with early clinical signs of disease (6). In the substantia nigra of PD patients, protective mechanisms are impaired and the brain is more susceptible to oxidants and reduced glutathione (GSH) -a potent antioxidantlevel is seen in these patinets. The combination of excessive oxyradical formation in an environment deficient in GSH and other defense pathways may be one of the primary mechanisms of neurodegeneration in PD (4, 5, 7, 8). A major hypothesis for the pathogenesis of PD is that neurotoxicity caused by free radicals leads to neuronal cell loss through overproduction of reactive oxygen and nitrogen species. Pharmacotherapy for PD improves patients’ symptoms, but its influence on neuroprotection has not yet been established. At the present time, no specific drug or supplement can be recommended for neuroprotection and for controlling the progression of PD (9-11). Our aim is to discuss agents that might have neuroprotective properties so that the selection of such drugs or supplements would be based on proper evidences.
Authors: Leila Kouti, Kaveh Eslami, Maryam Noroozian
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2261245158