ARMS/Kidins220 regulates nociception by controlling brain-derived neurotrophic factor secretion.

Pain is an alarm mechanism to prevent body damage in response to noxious stimuli. The nerve growth factor (NGF)/TrkA axis plays an essential role as pain mediator, and several clinical trials using antibodies against NGF have yielded promising results, but side effects have precluded their clinical approval. A better understanding of the mechanism of NGF/TrkA-mediated nociception is needed.

Regulation of BDNF Release by ARMS/Kidins220 through Modulation of Synaptotagmin-IV Levels.

BDNF is a growth factor with important roles in the nervous system in both physiological and pathological conditions, but the mechanisms controlling its secretion are not completely understood. Here, we show that ARMS/Kidins220 negatively regulates BDNF secretion in neurons from the CNS and PNS. Downregulation of the ARMS/Kidins220 protein in the adult mouse brain increases regulated BDNF secretion, leading to its accumulation in the striatum.

A Review on Ubiquitination of Neurotrophin Receptors: Facts and Perspectives.

Ubiquitination is a reversible post-translational modification involved in a plethora of different physiological functions. Among the substrates that are ubiquitinated, neurotrophin receptors (TrkA, TrkB, TrkC, and p75) have been studied recently. TrkA is the most studied receptor in terms of its ubiquitination, and different E3 ubiquitin ligases and deubiquitinases have been implicated in its ubiquitination, whereas not much is known about the other neurotrophin receptors aside from their ubiquitination.

Role of the sugar moiety on the opioid receptor binding and conformation of a series of enkephalin neoglycopeptides.

Glycosylation by simple sugars is a drug discovery alternative that has been explored with varying success for enhancing the potency and bioavailability of opioid peptides. Long ago we described two O-glycosides having either β-Glucose and β-Galactose of (d-Met, Pro)-enkephalinamide showing one of the highest antinociceptive activities known. Here, we report the resynthesis of these two analogs and the preparation of three novel neoglycopeptide derivatives (α-Mannose, β-Lactose and β-Cellobiose).