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| NEUROSCIENCE | ARTICLE


Melatonin and Parkinson’s disease Melatonin and its kynuramine metabolite interact directly with the electron transport chain, increasing electron flow and reducing electron leakage, and thereby increasing the survival of neurons under enhanced oxidative stress28


. As a result, memory and brain function


are improved owing to a decrease in brain oxidation29 anti-apoptotic effects30


, and blocked α-Synuclein fibril


formation, as well as destabilising preformed α-Synuclein fibrils. Subsequent evaluations have shown that melatonin was able to inhibit protofibril formation, oligomerisation, and secondary structure transitions. Importantly, melatonin also decreases α-Synuclein-induced cytotoxicity31, 32


.


Neuropeptide Y and neurodegenerative diseases In physiological conditions NPY modulates the release of a number of neurotransmitters, such as glutamate, GABA, noradrenaline, dopamine, somatostatin, serotonin, and corticotropin-releasing factor. In conditions such as AD, HD and PD, NPY decreases and does not inhibit glutamate release33


. Glutamate is the neurotransmitter of a number


increasing intellectual activity, and through a healthy diet and physical exercise. These processes produce a mild stress response in the cells, which increases protein production, growth factors and chaperones, all of which decrease oxidative stress and balance calcium homeostasis, ultimately resulting in neuronal survival, neuritis outgrowth, synaptic plasticity, learning and memory26


neuronal circuit, activating signalling pathways and increasing demand of energy, inducing gene protein expression; a healthy diet reduces glycaemia; and physical exercise increases energy demand, all driving a mild stress response.


Melatonin and neurodegenerative diseases


Melatonin and Alzheimer’s disease Melatonin and its kynurenine metabolites are membrane, cytosolic and nuclear antioxidants, particularly in neuronal tissues, are regulators of mitochondrial energy, prevent oxidative/nitrosative stress, inhibit the lethal effects of septic shock, prevent the reperfusion phenomenom, antagonise amyloid-β toxicity, and have anti-fibrillogenic actions in the presence of ApoE44


.


Melatonin-restoring disruption of sympathetic regulation of pineal melatonin changes during the early stages of AD. Reactivation of the circadian system by means of light therapy and melatonin supplementation has shown promising results27


.


Glutamate is the


. Intellectual activity increases activity in


neurotransmitter of a number of important pathways,


including cortical association fibres, corticofugal


pathways, and hippocampal,


cerebellar, and spinal cord


pathways.


of important pathways, including cortical association fibres, corticofugal pathways, and hippocampal, cerebellar, and spinal cord pathways. The excitatory actions of glutamate are mediated by multiple, distinct receptor types and receptor antagonists have recently been developed. Glutamate also has neurotoxic properties and can produce ÔexcitotoxicÕ lesions reminiscent of human neurodegenerative disorders. Abnormally enhanced glutamatergic neurotransmission may cause excitotoxic cell damage and lead to the neuronal death associated with HD. Pharmacologic manipulation of the glutamatergic system may have great potential for the rational treatment of a range of neurological diseases34


. NPY and NPY receptors may represent


pharmacological targets in different pathophysiological conditions33


. A neuroprotective role for NPY has been


suggested. NPY inhibits glutamate release evoked by the hippocampal nerve terminals and has a neuroprotective effect in rat organotypic hippocampal cultures exposed to an excitotoxic insult. Furthermore, changes in NPY levels have been observed in neurodegenerative diseases33


.


Insulin and neurodegeneration High insulin levels and insulin resistance are linked to obesity, diabetes, cardiovascular disease and neurodegenerative disease. Dysregulation of the insulin receptor substrate 2 proteins (IRS2) is the possible molecular link between diabetes neurodegenerative disease35


and . Many insulin responses


are directly integrated with counterregulatory hormones and proinflammatory cytokines through tyrosine and serine phosphorylation of IRS1 and IRS236


.


A diet rich in fruit and vegetables, low glycaemic charge and low in saturated fats decreases the risk for AD and cognitive deficit37


. prime-journal.com | June 2012 ❚ 51


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