A significant proportion of the hypothalamic neurons producing orexin, a neuropeptide involved in the regulation of sleep-wake rhythms, disappears in Parkinson’s disease.
Researchers from Etienne Hirsch’s team at the ICM have demonstrated a direct interaction of these neurons with substantia nigra dopaminergic neurons, those ones which loss causes the motor disturbances characteristic of the disease.
These researchers also discovered that orexin acted as a survival factor for dopaminergic neurons by a mechanism involving a specific receptor.
These observations suggest that a therapeutic approach to restore orexin neurotransmission in PD patients could halt the progression of the disease.
Bensaid M, et al. Sparing of orexin-A and orexin-B neurons in the hypothalamus and of orexin fibers in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated macaques. Eur J Neurosci. 2015; 41:129-36.
Guerreiro S, et al. The sleep-modulating peptide orexin-B protects midbrain dopamine neurons from degeneration, alone or in cooperation with nicotine. Mol Pharmacol. 2015; 87:525-32.