The Inflammatory Cytokines in the Pathogenesis of ParkinsonÃ¢ÂÂs Disease
Hanaa L Sadek, Sayedah F Almohari, and Waleed M Renno*
Department of Anatomy, Faculty of Medicine, Kuwait University, Kuwait
- Corresponding Author:
- Waleed M Renno
Department of Anatomy, Faculty of Medicine
Kuwait University, 24923, Safat 13110, Kuwait
Tel: 00965 2463 6283
Fax: 00965 25319478
E-mail: [email protected]
Received date: February 10, 2014; Accepted date: April 20, 2014; Published date: May 20, 2014
Citation: Sadek HL, Almohari SF, Renno WM (2014) The Inflammatory Cytokines in the Pathogenesis of Parkinson’s Disease. J Alzheimers Dis Parkinsonism 4:148. doi:10.4172/2161-0460.1000148
Copyright: © 2014 Sadek LH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopamine neurons in the substantia nigra pars compacta. Research and clinical data suggest that the etiology of PD is multifactorial. However, recent studies indicate that neuroinflammation and associated infiltration of inflammatory cells, chemokines and cytokines may play a critical role in the pathogenesis of PD. Cumulative evidences suggest that cytokines activation and neuroinflammation may have deleterious effects on the dopaminergic system and are key factors contributing to disease progression. The levels of proinflammatory cytokines in peripheral blood tend to be higher in PD patients. Studies of brains from PD patients and animal models have provided evidence for neuroinflammation, including activation of microglia, release of IFN-γ and TNF-α and infiltration of the midbrain by CD4 and CD8 lymphocytes. However, the influence of proinflammatory factors on the risk of PD remains unclear. In this review, we attempt to discuss the most recent publications on the role of inflammatory factors in PD. One hypothesis concerning the cause of degeneration of the nigrostriatal dopaminergic neurons is that PD is triggered by programmed cell death (apoptosis) due to increased levels of cytokines, apoptosis-related proteins and/or to decreased levels of neurotrophins such as brain-derived neurotrophic factor. Astrocytes stimulated by neuro-derived α-synuclein synthesize and release a number of proinflammatory cytokines and chemokines that in turn recruit and activate microglia. Thus, the effects of small amounts of neuronal α-synuclein protein can be amplified and sustained, thereby establishing an inflammatory microenvironment and further damaging neurons. This neuroprotection was shown to be associated with the anti-inflammatory properties of drugs that act as PPAR-γ agonists. In addition, these studies suggest that molecules that prevent inflammation and apoptosis may be useful in preventing or treating PD. In conclusion, protection of neurons against inflammation may help in slowing the neuronal degeneration in PD.