Some important characteristics of melatonin, changes in memory, inhibition of protein 2A phosphatases and its effect on tau, neurofilamentos and oxidative stress are reviewed in this document.
Melatonin (Mel) is a derivative of tryptophan, synthesized mainly in the pineal gland from the serotonin in the absence of light stimuli. It has maximum serum concentrations in the early morning, about four. They have designated it an important role in the regulation of various biological functions, circadian rhythms, sleep, mood, tumor growth and aging. Is a powerful scavenger of free radicals and also has been shown the modulator effect direct activity of kinases and protein phosphatases.
Fig 1 Dark memory.
Inhibition of proteins phosphatases in PP-2A and PP-1 by calyculin A (Cl-A) produces in cellular tissues and in vivo synaptic loss and deterioration of retention in the spatial memory through tau hyperphosphorylation and neurofilaments (NFs). The synaptophysin is a synaptic vesicular protein with important properties in the regulation of the activity-dependent synaptic formation, their levels are lowered by the action of Cl-A.
The cytoeskeletal protein tau and the neurofilaments hyperphosphorylation, synaptic loss, and memory deficits are characteristic of Alzheimer's disease (Alz). hyperphosphorylation reduces the balance of the micrutubules and influences cell organization and stability. Currently there is no effective cure against its pathology and memory impairment.
Previous studies demonstrated efficient mitigation of damage similar to Alz induced by the Cl-A through the Mel, not only because of its antioxidant effect but also for the regulation of the system of phosphorylation. As a result, it is appropriate establish the scenario where the Mel has neuroprotective effects in vivo against pathological effects similar to the Alz and spatial memory impairment by Cl-A. Therefore, protein phosphatases are considered a good therapeutic site for the treatment of the Alz.
Qing Tian et al. (2011) evaluated the effects of repeated pretreatment in vivo on laboratory animals via i.p., with Mel at low doses of 1 mg/kg and high of 10 mg/kg. They noted Mel protection in memory against the action of inhibitor Cl-A, the loss of synaptophysin in hippocampus and memory deficits retention prevention, as well as the improvement of the hyperphosphorylation of tau and neurofilaments. No significant difference in the two levels of dose exists. In addition, during the single administration to the established dose were absent evident consequences.
Mel partially reversed the effects of the Cl-A in phosphorylation of the catalytic unit of PP-2A in tyrosine 307, a crucial amino acid in negative regulation of activity of PP-2A, and decreased levels of malondialdehyde, an indicator of oxidative stress.
From preclinical studies and cellular systems, it is suggested the effectiveness of Mel as a therapeutic agent in the Alz and his unusual conduct via modulation of the activity of PP-2A and oxidative stress. In addition to reverse hyperphosphorylation of tau and NFs, loss of synapses and memory by Cl-A impairment.
Journal reference:
Qing Tian. (2011). Melatonin ameliorates Alzheimer-like pathological changes and spatial memory retention impairment induced by calyculin A. J Psychopharmacol August vol. 25 no. 8 1118-1125.
http://jop.sagepub.com/content/early/2010/06/10/0269881110367723
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