Sandbox Reserved 1109: Difference between revisions
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== Disease == | == Disease == | ||
Parkinson's disease (PD) is the most common neurodegenerative disorder affecting more than 10 Million Worldwide <ref>(https://www.parkinson.org/Understanding-Parkinsons/Statistics)</ref>. One of the main characteristics of Neurodegenerative disorders is the loss of the protective capacity surrounding the neurons or the gain of the toxic proteins. The mechanism by which the neuronal damage occurs is due to specific mutations, or other alterations of the synaptic proteins. Recently, it has been found that α-synuclein protein is the main component of Lewy bodies and Lewy neurites which are defining pathological characteristics of all Parkinson's disease cases. <ref>https://doi.org/10.1038/35081564</ref>. | Parkinson's disease (PD) is the most common neurodegenerative disorder affecting more than 10 Million Worldwide <ref>(https://www.parkinson.org/Understanding-Parkinsons/Statistics)</ref>. One of the main characteristics of Neurodegenerative disorders is the loss of the protective capacity surrounding the neurons or the gain of the toxic proteins. The mechanism by which the neuronal damage occurs is due to specific mutations, or other alterations of the synaptic proteins. Recently, it has been found that α-synuclein protein is the main component of Lewy bodies and Lewy neurites which are defining pathological characteristics of all Parkinson's disease cases.<ref>https://doi.org/10.1038/35081564</ref>. | ||
==Mechanism of aggregation== | ==Mechanism of aggregation== | ||
Parkinson's disease is characterized by the accumulation of Lewy bodies in the substantia nigra, a region in the midbrain responsible for motor control, where Lewy bodies contain a build-up of α-synuclein found within the cells that contribute to the disease <ref>PMID: 9546347<ref> Lewy Bodies are cytoplasmic inclusion made of primarily α-synuclein protein, and may also contain other proteins such as; ubiquitin, Tau proteins. The structure of α-synuclein; N-terminal domain, C-terminal domain, and a hydrophobic core (NAC) suggests an aggregation pathway due to the unfolded nature of the protein. A recent study published by the in Science Translational Medicine Journal, suggests that a covalent modification such as Serine-129 phosphorylation in α-synuclein, as well as hydrophobic interactions specifically located at the NAC domain of α-synuclein allows for the polymerization of different α-synuclein protein into an anti-parallel β-sheet conformation permitting the formation of fibrils. The role of α-synuclein in the pathogenesis of PD is mediated through the formation of the 58-83 KD complex that contains α-synuclein and 14-3-3 protein, which inhibits BCL-BAD protein complex responsible for the inhibition of Apoptosis.<ref>doi: 10.1126/scitranslmed.3002566</ref> However, it is important to know that the pathway discussed above is one of many hypotheses for the role of α-synuclein in Parkinson's Disease (PD). | Parkinson's disease is characterized by the accumulation of Lewy bodies in the substantia nigra, a region in the midbrain responsible for motor control, where Lewy bodies contain a build-up of α-synuclein found within the cells that contribute to the disease <ref>PMID: 9546347<ref> Lewy Bodies are cytoplasmic inclusion made of primarily α-synuclein protein, and may also contain other proteins such as; ubiquitin, Tau proteins. The structure of α-synuclein; N-terminal domain, C-terminal domain, and a hydrophobic core (NAC) suggests an aggregation pathway due to the unfolded nature of the protein. A recent study published by the in Science Translational Medicine Journal, suggests that a covalent modification such as Serine-129 phosphorylation in α-synuclein, as well as hydrophobic interactions specifically located at the NAC domain of α-synuclein allows for the polymerization of different α-synuclein protein into an anti-parallel β-sheet conformation permitting the formation of fibrils. The role of α-synuclein in the pathogenesis of PD is mediated through the formation of the 58-83 KD complex that contains α-synuclein and 14-3-3 protein, which inhibits BCL-BAD protein complex responsible for the inhibition of Apoptosis.<ref>doi: 10.1126/scitranslmed.3002566</ref> However, it is important to know that the pathway discussed above is one of many hypotheses for the role of α-synuclein in Parkinson's Disease (PD). | ||
