A brief history of hypocretin/orexin and narcolepsy.

The hypothalamic peptides named the orexins, or hypocretins, were discovered in 1998. In 1999 it was established that genetic narcolepsy could be caused by mutations in the genes synthesizing these peptides or their receptors. In September of 2000 it was found that most human narcolepsy is caused by loss of hypocretin cells, most likely as a result of a degenerative process. This paper reviews these events and their implications for our understanding of brain arousal and motor control systems.