Alpha-Synuclein (α-syn): Difference between revisions
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== Introduction == | == Introduction == | ||
Alpha-synuclein (α-syn) is a small protein encoded by the SNCA gene (the gene that provides instructions for α-syn). It is amply expressed in the nervous system and exists in a natively unfolded state under normal physiological conditions (however its conformation changes depending on its environment and interactions with binding partners). | |||
== | α-syn is abundant in the brain, and smaller amounts are found in the heart, muscles, and other tissues. In the brain, α-syn is found mainly at the tips of neurons in the specialized structures known as presynaptic terminals. Presynaptic terminals release neurotransmitters (chemical messages), from synaptic vesicles. In a healthy nervous system, α-syn is involved in transmission between neurons, helping signals move throughout the nervous system and within the brain. This allows for coordinated movement, proper control of bodily functions, and overall normal brain function. | ||
== Misfolding == | |||
For our body to function correctly our proteins are folded neatly into a shape that allows them to do their jobs . Proteins that are structured incorrectly usually are flagged and then fixed or thrown away. This is a complicated job involving enzymes, chaperones, and small factories or organelles, all monitoring the protein shape. This network helps prevent the formation of sticky piles of protein (known as aggregates) that cause disarray to our cells. | |||
However, the presence of genetic mutations or simply aging can make the protein surveillance system less effective, and this allows proteins for example α-syn to turn nasty, folding into an incorrect shape that cannot be fixed. If the neuron is unable to fix or dispose of the wrong shape, a whole a cascade of protein-misfolding occurs results in a sticky pile of α-syn. This causes havoc to the the normal neuronal function, creating debris that the neuron may not be able to clean up. | |||
Many conditions can promote this transition from soluble, functional α-syn into insoluble aggregates, and once this process begins, it proceeds in a feed-forward manner in aggregates form and seed and recruit soluble α-syn into more aggregates, a process that once escalated is largely irreversible. | |||
While α-syn oligomers and aggregates have not been proven to be directly toxic, they are consistently associated with toxicity. Within PD and other synucleinopathies, α-syn transforms from a soluble, functional protein to aggregated protein (i.e., LBs) that becomes associated with pathogenic results. | |||
== Sub Heading 3 == | == Sub Heading 3 == | ||
Revision as of 03:39, 16 September 2022
Original Editor - Lucinda hampton
Top Contributors - Lucinda hampton and Uchechukwu Chukwuemeka
Introduction[edit | edit source]
Alpha-synuclein (α-syn) is a small protein encoded by the SNCA gene (the gene that provides instructions for α-syn). It is amply expressed in the nervous system and exists in a natively unfolded state under normal physiological conditions (however its conformation changes depending on its environment and interactions with binding partners).
α-syn is abundant in the brain, and smaller amounts are found in the heart, muscles, and other tissues. In the brain, α-syn is found mainly at the tips of neurons in the specialized structures known as presynaptic terminals. Presynaptic terminals release neurotransmitters (chemical messages), from synaptic vesicles. In a healthy nervous system, α-syn is involved in transmission between neurons, helping signals move throughout the nervous system and within the brain. This allows for coordinated movement, proper control of bodily functions, and overall normal brain function.
Misfolding[edit | edit source]
For our body to function correctly our proteins are folded neatly into a shape that allows them to do their jobs . Proteins that are structured incorrectly usually are flagged and then fixed or thrown away. This is a complicated job involving enzymes, chaperones, and small factories or organelles, all monitoring the protein shape. This network helps prevent the formation of sticky piles of protein (known as aggregates) that cause disarray to our cells.
However, the presence of genetic mutations or simply aging can make the protein surveillance system less effective, and this allows proteins for example α-syn to turn nasty, folding into an incorrect shape that cannot be fixed. If the neuron is unable to fix or dispose of the wrong shape, a whole a cascade of protein-misfolding occurs results in a sticky pile of α-syn. This causes havoc to the the normal neuronal function, creating debris that the neuron may not be able to clean up.
Many conditions can promote this transition from soluble, functional α-syn into insoluble aggregates, and once this process begins, it proceeds in a feed-forward manner in aggregates form and seed and recruit soluble α-syn into more aggregates, a process that once escalated is largely irreversible.
While α-syn oligomers and aggregates have not been proven to be directly toxic, they are consistently associated with toxicity. Within PD and other synucleinopathies, α-syn transforms from a soluble, functional protein to aggregated protein (i.e., LBs) that becomes associated with pathogenic results.
Sub Heading 3[edit | edit source]
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