Parkinson's disease: A Review about Pathogenesis, Pharmaceutical Treatment and Experimental Models

Abstract

Parkinson disease (PD) is the second most common age-related neurodegenerative disease after Alzheimer disease, characterized by loss of dopaminergic neurons in substantia nigra pars compacta, accompanied by motor and non-motor symptoms. Idiopathic PD is the most common cause of Parkinsonism (primary Parkinsonism) while, certain medication and different groups of neurological disorder may be causes of secondary Parkinsonism. The presence of intraneuronal proteinaceous cytoplasmic inclusions “Lewy Bodies” and the loss of the nigrostriatal dopaminergic neurons are the main neuropathological hallmarks of PD. However, the etiology of the disease is still undefined; several studies assume that oxidative stress, mitochondrial defects, neuroinflammation, apoptosis and excitotoxicity play vital roles in the pathogenesis and progress of the disease. Experimental models of PD can be induced by several neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 6-hydroxydopamine, rotenone and paraquat which produce neuropathological and neurochemical changes that are identical to those seen in PD. The primary drug for PD treatment is L-dopa; however, drug-induced dyskinesia and motor complications restricted its use as long term treatment. Dopamine agonists are alternative options for initial treatment of PD and have been reported to retard the onset of motor complications. Combination of L-dopa with other medications, such ascatechol-O-methyltransferase inhibitors and monoamine oxidase B inhibitors has the ability to alleviate L-dopa-induced motor complications. Anticholinergic drugs can be used to control the symptoms of PD but their cognitive and autonomic side effects make them unsuitable for the elderly.