L’Accademia del Fitness groups which are able to facilitate movements through dopamine secretion; such pathological event has its clinical correspondent in the typical triad which defines Parkinson’s disease: • Bradykinesia: definition of the reduction of autonomous and voluntary mobility unaccompanied by a reduction of muscular power; • Rigidity: of asymmetric, plastic type due to which a patient affected by this disease has the sensation of “bending a lead pipe” or of modelling wax if he tries to lift a limb; • Trembling: at rest, at 4-6 cycles per second, begins in the distal limb sections. Many histological analytic studies on patients showing the first symptoms and on post-mortem tissues of substantia nigra of patients with diagnosed PD inform us that there are deficiencies inside the complex I of the electron transport chain.
Mitochondria involved in Parkinson’s disease, potential therapeutic efficacy of creatine in Parkinson’s. This disease is characterised by the damage of the complex I of mitochondrial electron transport chain (1). The suppression/ inhibition of complex I by neurotoxin MPTP diminishes the production of ATP, thus diminishing the ATP quantity which can be used by the PCr generated by mtCK (2). The damage to the electron transport chain increases the production of ROS, affecting the change of mtCK from an octameric to a dimeric shape making it inactive. Moreover, high ROS concentrations reduce CK cytosolic activity. Exogenous Cr intake brings about a general improvement of the cellular and mitochondrial bioenergy functions and increases the supplies of PCr which reduces the loss of neurons associated to Parkinson’s disease. In order to study and consolidate the role of mitochondria in Parkinson’s disease, neurotoxin MPTP (1-metyl-4-phenyl-1,2,3,6tetrahydropyridine) has been utilized as it damages mitochondrial functions and determines PD development in utilized human and animal models. Exposition to MPTP damages the complex I of the electron transport chain and is highly selective of dopaminergic neurons of the substantia nigra (SN) region. Moreover, MPTP easily penetrates through the haemato-encephalic barrier and, when they are inside the glial cells, the
MAO-B oxidise it into MPP+ (1-metyl-4-phenylpiridine). This compound penetrates the dopaminergic cells, in the substantia nigra area, exploiting the dopamine carrier. This causes the death of the neuron due to mitochondrial respiration inhibition, and also causes oxidative stress, which generates further damage. The effect of creatine combined with protector agent CoQ10 has been studied as an experimental model in rodents in which Parkinson’s disease was induced by means of MPTP intake. A 2% creatine and 1% CoQ10 supplement was added in the diet of some of the rodents for 2 weeks, whereas some other groups were not submitted to any at all or the two substances were submitted separately. After 28 days of this therapy, a significant decrease (56%) of the total striatal dopamine was seen in the group of rodents which had not received Cr and CoQ10; there was instead a significant reduction of dopamine depletion (33%) induced by MPTP in the mice treated with the diet integrated with Cr and CoQ10. The diet supplements consisted either in 2% creatine or 1% CoQ10 intake or a mix of both substances. Intake of both substances significantly reduced the MPTP negative effect on dopamine production, thus proving to be the best treatment.
Neuroprotective effect of creatine integrated with CoQ10 in reducing neurodegenerative effects on nigrostriatal dopaminergic neurons induced by toxin MPTP. (A) Cr and CoQ10 significantly reduce depletion caused by MPTP of striatal dopaminergic neurons. (B) Quantity of cells present and quantity of TH (tyrosine hydroxylase) present in dopaminergic neurons of SNpc. Intake of Cr and CoQ10 drastically reduce loss of neurons caused by MPTP. (C)Photomicrography of SNpc section of rodent, creatine and CoQ10 inhibit loss of neurons producing TH induced by MPTP. Immunohistochemical analysis of Substantia Nigra Pars Compacta (SNpc) dopaminergic neurons demonstrated that, after 28 days of MPTP treatment, there was a heavy loss of tyrosine hydroxylase (TH) enzyme functionality. This enzyme adds a hydroxyl group (-OH) in position 3’ to Tyrosine to produce the compound L-DOPA (Levodopa).
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