Alpha-synuclein and parkinson [?-si·nüklei·n ve parki·nson]

Abstract

Parkinson disease is an age-related disorder. It was seen all part of society. It is existed by genetic predisposition and different effects. The disease usually starts insidously and its symptoms progress slow but causing acceleration. Middle brain gets narrow according to normal brain in Parkinson, pigmentation is decreased in substantia nigra pars compacta, loss of dopaminergic neurons which produce dopamine and Lewy body formation are observed. Accumulation of formation-like cc-synuclein which plays formation of Lewy body, causes dopaminergic neuron losses by 50-60 % and so that mistakes of dopamine releasing prevent neuron transmission. It is seen that symptoms of Parkinson and Parkinson-like neurodegenerative disorders which have signs like shaking, defeat of posture, slowing of understanding, senile, hard to see, hard to smell, are increasing day by day. ?-synuclein is expressed in especially subtantia nigra pars compacta in middle brain, hypocampus, amyglada and cerebral cortex areas. After ?-synuclein which is presinaptic protein, is expressed cytoplasma of neuron which have many presynaptic ends, is moved axon ends. Mutation which is determined in gene where codes cc-synuclein protein, is first gene mutation which causes Parkinson, ?-synuclein protein which is coded by ?-synuclein gene in 4q21-22 human chromosome contains 140 amino acid residuses. ?-synuclein have important roles at stages of neuronal life. They play important roles in physiologically arrangement of neurotransmitter vesicul, transporters and certain enzymes and transporting fatty acids in neuron cytoplasm. It participates dopamine biosynthesis and protection of dopamine balance. It also functions axonal transport. In addition, ?-synuclein controls expression of secretion vesicul. ?-synuclein is tranformed into its pathological forms by lossing its normal structure as a consequence of several factors. Pathological ?-synuclein forms also cause Parkinson by acting effective role in neuron degeneration. Oligomer formation from pathological ?-synuclein forms, don't damage neuron cell until a stage. If they change fibrile by increasing oligomer forms with protofibril which doesn't change fibrile, accumulate body of neuron and axon ends, participate formation of Lewy body. Lewy bodies act effective role in neuron pathology and Parkinson development. The other factors which are effective in neuron pathology are oxidative stress, over-produce, low pH, high temperature, injuries in destruction, mutations of ?-synuclein gene among them. There are important studies about A53T, A30P and E46K missense mutations in ?-synuclein gene which induces Parkinson. These mutations cause Lewy body aggregations by changing of ?-synuclein to fibril formation and showing its effects different way. A30P mutations impair vesicul membrane binding of ?-synuclein which contains dopamine by causing changes in three dimension of ?-synuclein. As a consequence, defects appear in releasing of dopamine and uptaking from dopamine vesicule. In conlusion, ?-synuclein gene mutations which cause defects in ?-synuclein metabolic pathway, and Lewy bodies which are formed by different effects with defects in producing and releasing of dopamine act effective role in Parkinson disease by causing damages in dopaminergic neuron with their death.