Synucleinopathy: Difference between revisions
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== Introduction == | == Introduction == | ||
[[File:Alpha-synuclein.png|thumb|748x748px|α-syn, a protein in the brain]] | [[File:Alpha-synuclein.png|thumb|748x748px|α-syn, a protein in the brain]] | ||
Synucleinopathies are a subgroup of [[Neurodegenerative Disease|neurodegenerative diseases]], characterised by impairment of alpha-synuclein (αSyn) metabolism, producing abnormal intracellular deposits (namely progressive aggregation of insoluble fibrillary αSyn in [[Neurone|neurons]] and [[Glial Cells|glia]]). All of them are [[Chronic Disease|chronic]], progressive disorders that lack a causal therapy.<ref name=":0">Radiopedia [https://radiopaedia.org/articles/synucleinopathy-1?lang=gb Synucleinopahy] Available | Synucleinopathies are a subgroup of [[Neurodegenerative Disease|neurodegenerative diseases]], characterised by impairment of alpha-synuclein (αSyn) metabolism, producing abnormal intracellular deposits (namely progressive aggregation of insoluble fibrillary αSyn in [[Neurone|neurons]] and [[Glial Cells|glia]]). All of them are [[Chronic Disease|chronic]], progressive disorders that lack a causal therapy.<ref name=":0">Radiopedia [https://radiopaedia.org/articles/synucleinopathy-1?lang=gb Synucleinopahy] Available | ||
Although the exact mechanism of initiation of aggregation and misfolding pathway of a-Syn is yet to be discovered; it’s mechanism of spreading through interconnected neuronal networks is a proposed theory. This theory suggests that a-Syn is released from the diseased cell and is then uptaken by normal adjacent cells. <ref name=":2">Kompoliti K, Verhagen L. Encyclopedia of movement disorders. Academic Press; 2010 Feb 26. Available: https://www.sciencedirect.com/topics/medicine-and-dentistry/synucleinopathies<nowiki/>(accessed 15.9.2022)</ref><ref>Huang D, Nazarova L. | from:https://radiopaedia.org/articles/synucleinopathy-1?lang=gb (accessed 15.9.2022)</ref><ref name=":1">Sympath Synucleinopathies Available from: http://archive.sympath-project.eu/synucleopathies/?lang=en (accessed 15.9.2022)</ref> | ||
Although the exact mechanism of initiation of aggregation and misfolding pathway of a-Syn is yet to be discovered; it’s mechanism of spreading through interconnected neuronal networks is a proposed theory. This theory suggests that a-Syn is released from the diseased cell and is then uptaken by normal adjacent cells. <ref name=":2">Kompoliti K, Verhagen L. Encyclopedia of movement disorders. Academic Press; 2010 Feb 26. Available from: https://www.sciencedirect.com/topics/medicine-and-dentistry/synucleinopathies<nowiki/>(accessed 15.9.2022)</ref><ref>Huang D, Nazarova L. <big>Misfolded α-syn–from release and uptake to contagion of adjacent cell, any links with gut?</big> Available from:http://www.ijsit.com/admin/ijsit_files/MISFOLDED%20SYN%20FROM%20RELEASE%20AND%20UPTAKE%20TO%20CONTAGION%20OF%20ADJACENT%20CELL%20ANY%20LINKS%20WITH%20GUT_IJSIT_10.5.7.pdf (accessed 15.9.2022)</ref> | |||
== Divisions Of Synucleinopathies == | == Divisions Of Synucleinopathies == | ||
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== Human Alpha-Synuclein (α-syn) == | == Human Alpha-Synuclein (α-syn) == | ||
Human alpha-synuclein (α-syn) is predominantly expressed in the [[Brain Anatomy|brain]], accounting for approximately 1% of brain weight. It is found chiefly in the neocortex, [[hippocampus]], [[Substantia Nigra|substantia nigra]], [[thalamus]], and [[cerebellum]], and is found in Lewy bodies (LBs). As well as accumulating in the brain, α-synuclein also accumulates in the gastrointestinal tract resulting in symptoms. <ref>Emamzadeh FN. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122110/ Alpha-synuclein structure, functions, and interactions.] Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences. 2016;21. | Human alpha-synuclein (α-syn) is predominantly expressed in the [[Brain Anatomy|brain]], accounting for approximately 1% of brain weight. It is found chiefly in the neocortex, [[hippocampus]], [[Substantia Nigra|substantia nigra]], [[thalamus]], and [[cerebellum]], and is found in Lewy bodies (LBs). As well as accumulating in the brain, α-synuclein also accumulates in the gastrointestinal tract resulting in symptoms. <ref name=":3">Emamzadeh FN. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122110/ Alpha-synuclein structure, functions, and interactions.] Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences. 2016; 21: 29. doi: 10.4103/1735-1995.181989</ref> <ref name=":0" /><ref name=":2" /> | ||
== Main Symptoms == | == Main Symptoms == | ||
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# Behavioral changes. | # Behavioral changes. | ||
Symptoms of these diseases significantly overlap with one another, hindering diagnosis. for example [[parkinsonism]] is the predominant symptom of PD. Still, it can be indistinguishable from the parkinsonism of LBD and MSA.<ref>MartÌ MJ, Tolosa E, Campdelacreu J. Clinical overview of the synucleinopathies. Movement disorders | Symptoms of these diseases significantly overlap with one another, hindering diagnosis. for example [[parkinsonism]] is the predominant symptom of PD. Still, it can be indistinguishable from the parkinsonism of LBD and MSA.<ref>MartÌ MJ, Tolosa E, Campdelacreu J. [https://pubmed.ncbi.nlm.nih.gov/14502652/ Clinical overview of the synucleinopathies]. Movement disorders. 2003 Sep;18(S6):21-7.</ref><ref name=":1" /> | ||
== Future Management == | == Future Management == | ||
[[File:Protein folding figure.png|thumb|455x455px|Protein folding figure]] | [[File:Protein folding figure.png|thumb|455x455px|Protein folding figure]] | ||
In healthy brain cells, correctly constructed alpha synuclein is typically found just inside the surface of the membrane surrounding the cell body and in the presynaptic terminals (critical to passing messages between neurons).<ref>The science of PD Alpha Synuclein Available: https://scienceofparkinsons.com/alpha-synuclein/ (accessed 15.9.2022)</ref> | In healthy brain cells, correctly constructed alpha synuclein is typically found just inside the surface of the membrane surrounding the cell body and in the presynaptic terminals (critical to passing messages between neurons).<ref>The science of PD Alpha Synuclein. Available from: https://scienceofparkinsons.com/alpha-synuclein/ (accessed 15.9.2022)</ref> | ||
The abnormal aggregation of α-synuclein has proved to be the “rosetta stone” of PD, DLB, and MSA. There is increasing evidence demonstrating the propagation of pathological α-Syn to be central to the pathogenesis of synucleinopathies, for example in PD and MAS.<ref name=":1" /><ref | The abnormal aggregation of α-synuclein has proved to be the “rosetta stone” of PD, DLB, and MSA. There is increasing evidence demonstrating the propagation of pathological α-Syn to be central to the pathogenesis of synucleinopathies, for example in PD and MAS.<ref name=":1" /><ref name=":3" /> | ||
Comprehending disease aetiology and pathogenesis is a start, but developing safe and effective mechanism-based treatments is the goal. For example, some pharmaceutical companies are focusing on compounds that prevent α-syn from aggregation. When mechanism-based therapies for PD, LBD, and MSA will become available, they will probably interfere with the neurodegeneration caused by the aggregation of α-synuclein.<ref>Goedert M, Jakes R, Spillantini MG. The synucleinopathies: twenty years on. Journal of Parkinson's disease. 2017 Jan 1;7(s1):S51-69. | Comprehending disease aetiology and pathogenesis is a start, but developing safe and effective mechanism-based treatments is the goal. For example, some pharmaceutical companies are focusing on compounds that prevent α-syn from aggregation. When mechanism-based therapies for PD, LBD, and MSA will become available, they will probably interfere with the neurodegeneration caused by the aggregation of α-synuclein.<ref>Goedert M, Jakes R, Spillantini MG. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345650/ The synucleinopathies: twenty years on]. Journal of Parkinson's disease. 2017 Jan 1;7(s1):S51-69.</ref> | ||
== References == | == References == | ||
Revision as of 14:39, 28 September 2022
Original Editor - Lucinda hampton
Top Contributors - Lucinda hampton, Uchechukwu Chukwuemeka, Kim Jackson and Angeliki Chorti
Introduction[edit | edit source]
Synucleinopathies are a subgroup of neurodegenerative diseases, characterised by impairment of alpha-synuclein (αSyn) metabolism, producing abnormal intracellular deposits (namely progressive aggregation of insoluble fibrillary αSyn in neurons and glia). All of them are chronic, progressive disorders that lack a causal therapy.[1][2]
Although the exact mechanism of initiation of aggregation and misfolding pathway of a-Syn is yet to be discovered; it’s mechanism of spreading through interconnected neuronal networks is a proposed theory. This theory suggests that a-Syn is released from the diseased cell and is then uptaken by normal adjacent cells. [3][4]
Divisions Of Synucleinopathies[edit | edit source]
The synucleinopathies can be divided into those with and those without the formation of Lewy bodies (however some overlap does exist) and include:
- Synucleinopathies with Lewy bodies: Parkinson disease (PD); Lewy body disease (LBD);
- Synucleinopathies without Lewy bodies: Multiple systemic atrophy (MSA); pure autonomic failure; rapid eye movement (REM) sleep behaviour disorder.[1]
This 4 minute video gives a introduction to the synucleinopathies
Human Alpha-Synuclein (α-syn)[edit | edit source]
Human alpha-synuclein (α-syn) is predominantly expressed in the brain, accounting for approximately 1% of brain weight. It is found chiefly in the neocortex, hippocampus, substantia nigra, thalamus, and cerebellum, and is found in Lewy bodies (LBs). As well as accumulating in the brain, α-synuclein also accumulates in the gastrointestinal tract resulting in symptoms. [6] [1][3]
Main Symptoms[edit | edit source]
Synucleinopathies are chronic disorders that develop gradually. Symptoms include:
- A decline in motor and cognitive functions
- Behavioral changes.
Symptoms of these diseases significantly overlap with one another, hindering diagnosis. for example parkinsonism is the predominant symptom of PD. Still, it can be indistinguishable from the parkinsonism of LBD and MSA.[7][2]
Future Management[edit | edit source]
In healthy brain cells, correctly constructed alpha synuclein is typically found just inside the surface of the membrane surrounding the cell body and in the presynaptic terminals (critical to passing messages between neurons).[8]
The abnormal aggregation of α-synuclein has proved to be the “rosetta stone” of PD, DLB, and MSA. There is increasing evidence demonstrating the propagation of pathological α-Syn to be central to the pathogenesis of synucleinopathies, for example in PD and MAS.[2][6]
Comprehending disease aetiology and pathogenesis is a start, but developing safe and effective mechanism-based treatments is the goal. For example, some pharmaceutical companies are focusing on compounds that prevent α-syn from aggregation. When mechanism-based therapies for PD, LBD, and MSA will become available, they will probably interfere with the neurodegeneration caused by the aggregation of α-synuclein.[9]
References[edit | edit source]
- ↑ 1.0 1.1 1.2 Radiopedia Synucleinopahy Available from:https://radiopaedia.org/articles/synucleinopathy-1?lang=gb (accessed 15.9.2022)
- ↑ 2.0 2.1 2.2 Sympath Synucleinopathies Available from: http://archive.sympath-project.eu/synucleopathies/?lang=en (accessed 15.9.2022)
- ↑ 3.0 3.1 Kompoliti K, Verhagen L. Encyclopedia of movement disorders. Academic Press; 2010 Feb 26. Available from: https://www.sciencedirect.com/topics/medicine-and-dentistry/synucleinopathies(accessed 15.9.2022)
- ↑ Huang D, Nazarova L. Misfolded α-syn–from release and uptake to contagion of adjacent cell, any links with gut? Available from:http://www.ijsit.com/admin/ijsit_files/MISFOLDED%20SYN%20FROM%20RELEASE%20AND%20UPTAKE%20TO%20CONTAGION%20OF%20ADJACENT%20CELL%20ANY%20LINKS%20WITH%20GUT_IJSIT_10.5.7.pdf (accessed 15.9.2022)
- ↑ Air to air. Synucleinopathy. Available from:https://www.youtube.com/watch?v=fz0lM2-JAo4 [last accessed 15/9/2022]
- ↑ 6.0 6.1 Emamzadeh FN. Alpha-synuclein structure, functions, and interactions. Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences. 2016; 21: 29. doi: 10.4103/1735-1995.181989
- ↑ MartÌ MJ, Tolosa E, Campdelacreu J. Clinical overview of the synucleinopathies. Movement disorders. 2003 Sep;18(S6):21-7.
- ↑ The science of PD Alpha Synuclein. Available from: https://scienceofparkinsons.com/alpha-synuclein/ (accessed 15.9.2022)
- ↑ Goedert M, Jakes R, Spillantini MG. The synucleinopathies: twenty years on. Journal of Parkinson's disease. 2017 Jan 1;7(s1):S51-69.
