Narcolepsy: Autoimmunity or Secondary to Infection?

Abstract

Narcolepsy is a sleep disorder that is characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucination, and sleep paralysis. In the review presented here, we aim at focusing on the immunological aspects of the disease. Special attention will be given to the link between tumor necrosis factor-α (alpha) (TNF) and major histocompatibility class II (MHC II) antigens and on autoimmunity, autoinflammation, and neuronal cell death. The latter may affect mainly neurons that produce hypocretin peptides (Hcrt-1 and Hcrt-2; also known as orexins A and B) and hypocretin receptors (Hcrtr-1 and Hcrtr-2). The involvement of this neurotransmitter pathway in narcolepsy is extensively discussed within this book. A mutation in the canine Hcrtr-2 gene or disruption of the prepro-hypocretin gene in knockout mice causes narcolepsy. In humans, only one patient with early onset of disease in childhood has been reported to have a mutation in the hypocretin genes. However, hypocretin concentration in the cerebrospinal fluid (CSF) of narcolepsy patients is decreased. This finding points to an abnormal expression of the Hcrt gene, or release of hypocretin in the disease. (PsycInfo Database Record (c) 2022 APA, all rights reserved)