Cytokines and Neurotrophins in Parkinson’s Disease: Involvement in Apoptosis

Abstract

Parkinson’s disease (PD) is characterized by deficiency of neurotransmitter dopamine (DA) in the nerve terminals of the nigrostriatal DA neurons in the substantia nigra pars compacta. Many factors are speculated to operate in the mechanism of cell death of the nigrostriatal DA neurons in PD, e.g., oxidative stress and cytotoxicity of reactive oxygen species (ROS), disturbance of intracellular calcium homeostasis, endogenous or exogenous neurotoxins, and mitochondrial dysfunctions especially in complex I of the electron transport system (Foley and Riederer, 1999). An association of altered immune responsiveness with PD that may be related to the programmed cell death (apoptosis) has also recently been speculated (Nagatsu & Mogi, 1998; Nagatsu et al., 1999; Mogi & Nagatsu, 1999c; Hirsch et al., 1999; Hartmann et al., 2000, 2001). We have obtained, specifically in the nigrostriatal DA regions of the postmortem brains of patients with PD as well as in animal models of PD, the following evidences suggestively implicating the immune response and apoptosis in PD.: (1) an increased neopterin/biopterin ratio in the cerebrospinal fluid (CSF) from patients with PD, (2) increased levels of beta2-microglobulin, the light chain of the major histocompatibility complex class I (MHC-I) molecules, (3) increased levels of proinflammatory cytokines such as TNF-alpha and IL-1 beta, (4) decreased levels of neurotrophins such as BDNF and NGF, and (5) increased levels of apoptosis-related proteins or increased activities of apoptosis-producing caspases.KeywordsSubstantia NigraJuvenile ParkinsonismParkinsonian BrainNerve Growth Factor ConcentrationImmunosuppressant FK506These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.