MINIREVIEW: The hypocretins and sleep
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چکیده
Observations on humans and experimental animals with localized hypothalamic lesions led to the earliest notions about the role of the lateral hypothalamus (LH). From studying patients with encephalitis lethargica, von Economo [1] proposed that the posterior hypothalamus (including the LH) was required for maintaining the awake state. The signaling molecules and circuitry responsible for this observation remained unknown until the discoveries of the hypocretin (Hcrt) and melanin-concentrating hormone (MCH) systems. Gautvik and colleagues [2] conducted a systematic subtractive hybridization survey aimed at identifying mRNA species whose expression was restricted to discrete nuclei within the rat hypothalamus. Among these was a species whose expression, as detected by in situ hybridization analyses, was restricted to the perifornical area in the dorsolateral hypothalamus [2,3] (Fig. 1). The 569 nucleotide sequence of the corresponding cDNA revealed that it encoded a 130 residue putative secretory protein with an apparent signal sequence and two additional phylogenically conserved sites for potential proteolytic maturation followed by modification of the carboxy-terminal glycines by peptidylglycine a-amidating monooxygenase [3]. These features suggested that the product of this hypothalamic mRNA served as a preprohormone for two C-terminally amidated, secreted peptides. These two peptides, 28 and 33 amino acids in length showed some similarity between each other at the C-terminus. The 33 residue peptide displayed a sequence of seven amino acids which is identical within the peptide secretin. Thus, we named the peptides hypocretins for their strict
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تاریخ انتشار 2005