Neurotensin as Modulator of Basal Ganglia- Thalamocortical Motor Circuit – Emerging Evidence for Neurotensin NTS1 Receptor as a Potential Target in Parkinson's Disease

摘要

This chapter is focused on the putative role of neurotensin in the development of Parkinson’s disease, a neurodegenerative disorder mainly characterized by a progressive loss of nigrostriatal dopaminergic neurons (Schimpff et al., 2001). Although a direct causal role of neurotensin in Parkinson’s disease has not yet clearly demonstrated, some convincing animal and human studies support the potential role of the peptide in the etiopathogenesis of this motor disorder. Special emphasis is placed on the significance that neurotensin plays on basal ganglia neuroplasticity and neurodegeneration. This is mainly supported by recent findings clearly demonstrating that neurotensin enhances glutamate excitotoxicity in mesencephalic dopamine neurons and that neurotensin receptors are involved in the modulation of NMDA-induced excitotoxicity (Antonelli et al., 2002; 2004). Through these mechanisms neurotensin could contribute to the development and/or the progression of neurodegenerative disorders. The possible use of neurotensin receptor antagonists, in combination with conventional therapy, in the treatment of Parkinson’s disease, is also discussed.