Parkinson’s disease, people over the age of 65 of approximately 2-3% affecting second most common neurodegenerative disease. In this disease, the part of the brain called the substantia nigra, a region of the brain is influenced by. In this region, neurotransmitters called dopamine synthesizing neurons in the lobby.
The neurons in the subtantia nigra Parkinson’s disease, alpha synuclein accumulation is a result of because the lack of dopamine will occur. Alpha-synuclein accumulation and the underlying mechanism of what? So far, according to the results of the studies, there can be several mechanisms that are responsible for this situation.
Alpha synuclein in neurons of substantia dopaminergic neurons in cigarettes alone outside of the loss or the accumulation of Parkinson’s diseases of the nervous system occurs. But the combination of these two situations is a sign of Parkinson’s disease.The loss of dopamine synthesizing neurons in substantia nigra in the early stages of the disease is limited to the region, but the disease spreads to other parts of the brain until the end of. Alpha-synuclein in the cytoplasm of certain neurons in several different brain regions that accumulate an abnormal amount of time.
The aggregate alpha of flies (many molecules connect to each other and to form insoluble structures) by Lewy bodies, which are large structures that creates a becoming, a century ago, was discovered for the first time. Histology following the development of methods in various ways alpha synuclein aggregates were observed. Lewy pathology initially, the neurons and brain stem neurons that belong to the olfactory sense will occur in. In limbic and neocortical regions of the brain as the disease progresses has been observed.Alzheimer’s pathology in patients with alpha-synuclein pattern varies, and are concentrated in limbic brain regions.
The hereditary form of Parkinson’s disease, of all cases only 5-10% is seen, although disease-related genes in Parkinson’s gives a hint as to the underlying mechanisms of neuro. A number of proteins encoded by certain genes are associated with Parkinson’s disease the molecular pathway that is associated with. When this pathway is disrupted noropatoloji similar to Parkinson’s disease. In addition, studies in Parkinson’s disease reveals that he was impressed by some of these genes.Examples of associated pathways: the balance of alpha synuclein, mitochondrial function, oxidative stress, calcium balance, and noroimflamasyon axonal transport.
All alpha synuclein aggregates between neurons in Parkinson’s disease patients was observed. Alpha-synuclein and the point mutations in the gene sequence SNCA the addition of alpha synuclein in the brain as a result of accumulation of hereditary and occurs in the form of Parkinson’s disease. Neurons derived from pluripotent stem cells of Parkinson’s patients evoked culture and post-mortem brain samples with SNCA synuclein Alpha gene variant increases risk in a study it was found that the expression of.
140 the amino acid (protein building blocks) in length alpha-synuclein protein in normal neural function is not fully understood. But it occurs in (intracellular fluid), probably mitochondria (cell organelles that produce energy in the main task) and in the nucleus of the cell occurs. Vesicle traffic between synapses in the function of mitochondria, cells and the traffic between a potential chaperone (proteins that ensures proper folding of the proteins) may serve as. During the process of pathological alpha-synuclein neurotoxic effect begins to show. For example;alpha synuclein under normal conditions of a water soluble molecule, while monomer (single molecule) oligomers with other molecules (many molecules of the same type connecting to each other) then takes the form it creates and insoluble fibril big porn movies (Lewy bodies) they become. Alpha-synuclein accumulation and aggregation may be a variety of trigger factors. For example, mutations in genes that encode the molecule, or the result of too much alpha synuclein alpha synuclein protein folds can be produced as a result of a gene mutation that can build up in the brain, folded up incorrectly.Aging, the reduction in the activity of the defense mechanism against the accumulation of protein, who served as alpha-can play an important role in the accumulation of single.
The balance between this molecule and cells, proteozom ubiquitin system (a molecule called ubiquitin to proteins that trashed the system and add them faulty) and otofaji lysosomal system (LAS) is provided. To clear accumulations oligomeric LAS ubiquitin proteome system is more important than appears. LAS, including chaperone-dependent alpha-synuclein is a catalyst for disintegration and microcephaly otofaji systems. Chaperone-dependent otofaji, lysosomes specific proteins that target specific chaperone to go to. Both systems increases the level of alpha synuclein suppression.This is proof that a stabilizing interaction between the two systems. Ubiquitin-protease system on the part of both the groups and non-proteases (protein destroying enzymes) are also alpha synuclein between cells in the space can tear apart.
The accumulation of alpha synuclein in this system that have led to the deterioration of the shredding of evidence. Parkinson’s disease increasing age is the greatest risk factor for falling and is associated with the ubiquitin system functions in Las proteozom. Thus, during the process of normal aging, dopamine synthesizing neurons in alpha-synuclein is the brig. Part of the substantia nigra of Parkinson’s patients and in experimental models, alpha-synuclein accumulated in neurons to decrease levels of lysosome enzymes, chaperone-mediated reduced otofaji and proteins accumulate.Other observations, changing the balance of protein that affects the accumulation of alpha-synuclein supports. For example, alpha-synuclein oligomers proteozom ubiquitin system, microcephaly, and chaperone-mediated otofaji suppresses the system. Dissecting alpha-synuclein protein accumulation in cells, accumulates in a deterioration in the system and this also renders the protein inactive shredding systems. As a result, these observations reveal the existence of a vicious cycle.
A couple of associated with the genetic form of Parkinson’s disease mutation is associated with decreased function of the Las. The g2019s mutation in the gene LRRK2 ,impaired function and increased dopamine synthesizing neurons in the Las alpha-synuclein accumulation is linked with. A lysosomal enzyme, which is ‘ The most common genetic risk factor of Parkinson’s disease is mutations in genes that encode and decreased function causes it to Las. In this study, two changes in the gene in the development of Parkinson’s disease and GBA GBA a steady decrease in activity was seen in the normal aging process.The accumulation of alpha synuclein in cell culture and animal models, both were accompanied by falling activity in the GBA. VPS35 mutations in genes that encode proteins named also leads to hereditary Parkinson’s disease. VPS35, a protein complex, as part of newly synthesized lipids and proteins of lysosomes or the Golgi apparatus acts in tending to. Found in lysosomes, a type of ATPase (ATP enzymes) mutations in the park9 gene encodes, Barber-Rakeb syndrome is associated with a neurological disease that is named. There are similar findings to this syndrome or Parkinson’s disease.LRRK2, and park9 mutations in the GBA genes, formed by these genes function in a common pathway supports the idea that perform.
Alpha-Synuclein Propagation In A Manner Similar To The Priors
Alpha-synuclein, which leads to the accumulation of additional mechanisms have recently appeared. PRIO (incorrect folding of proteins in the brain and spreading) according to the hypothesis that looks like alpha synuclein, alpha-synuclein can spread to different parts of the brain via the axons of neurons and the cells may continue to accumulate in the space between. Cell culture studies on the mechanism of Las is damaged in the case where alpha-synuclein accumulates in the space between cells. Thus, a small amount of initially incorrectly folded in the cell, alpha-synuclein protein, multiple regions of the brain during the years of eruptions.This model of alpha-synuclein aggregates first began to occur in the first place the bowel nerves and the olfactory area in the brain, when the symptoms can be in the final stages before it spreads supports the idea that leads to disturbances in the substantia nigra.
The accumulation of alpha synuclein was seen in the same cycle, alpha-synuclein accumulation and mitochondrial disorders will occur. In the electron transport chain (aerobic respiration the reactions of a Stage) Complex 1 in the mitochondria the activity of tissues of Parkinson’s disease patients. The decrease in the activity of this gene and oxidative stress in mitochondria leads to the accumulation of alpha synuclein.
Today, along with the prolongation of life expectancy, the incidence of neurodegenerative diseases has increased. Therefore, the mechanism of therapeutic manipulation of these mechanisms and the disclosure of such diseases have gained considerable importance. Work to be done on this topic in the future, you may be able to maintain brain health even in advanced age.
Poewe et al. In Parkinson’s disease. Nature Reviews. doi:10.1038/nrdp.2017.Thirteen