Roles of cocaine- and amphetamine-regulated transcript in the central nervous system.

1. Cocaine- and amphetamine-regulated transcript (CART), first isolated from the ovine hypothalamus, is a potential neurotransmitter widely distributed throughout the central and peripheral nervous systems, as well as in endocrine cells in the pituitary and adrenal glands, pancreatic islets and stomach. 2. Numerous studies have established the role of CART in food intake, maintenance of bodyweight, stress control, reward and pain transmission. Recently, it was demonstrated that CART, as a neurotrophic peptide, had a cerebroprotective against focal ischaemic stroke and inhibited the neurotoxicity of β-amyloid protein, which focused attention on the role of CART in the central nervous system (CNS) and neurological diseases. 3. In fact, little is known about the way in which CART peptide interacts with its receptors, initiates downstream cascades and finally exerts its neuroprotective effect under normal or pathological conditions. The literature indicates that there are many factors, such as regulation of the immunological system and protection against energy failure, that may be involved in the cerebroprotection afforded by CART. 4. The present review provides a brief summary of the current literature on CART synthesis and active fragments, its distribution in the CNS and, in particular, the role of CART peptide (and its receptors and signalling) in neurological diseases.