The role of monoamines in the development of Alzheimer's disease and neuroprotective effect of a proline rich polypeptide

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Introduction:We have analyzed the alterations in the brain monoaminergic system using the rat model of AD-like pathology. In addition, we have investigated potential neuroprotective effects of the hypothalamic proline-rich polypeptide (PRP-1).Methods:Histochemical staining, HPLC, chemiluminescent and bioluminescence assays.Results:The levels of monoamines in the target AD brain structures were found elevated, except serotonin, which was unaffected in both hippocampus and brainstem and decreased in frontal cortex. This was accompanied by the substantial structural damage of cortical, hippocampal, as well as the monoaminergic neurons of locus coeruleus and oxidative stress. PRP-1 was able to reverse most of these changes.Discussion:The increased levels of major brain monoamines in the model of AD supports the hypothesis of the important role of monoamines in the excessive synaptic excitation resulting in cognitive dysfunction in AD brain. The neuroprotective effect of PRP-1 as manifested by the recovery of monoaminergic system suggests this bioactive compound as a perspective therapeutic agent for the treatment of AD.HighlightsBrain monoamines were found elevated in the rat model of AD.This was associated with the structural damage of monoaminergic neurons.The level of oxidative stress was found enhanced in the same brain structures.Data support monoamines role in the excessive synaptic excitation in AD brain.Bioactive PRP-1 reverses these changes suggesting a novel agent for AD treatment.

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