Considering Autoimmune cross-targeting as the trigger of Parkinson's, two infections on one target where a virus is inside and a larger infection is outside. Why do we see the characteristics we see for parkinson's disease?
Hypothesis: The pathways of the receptor used by the virus causes the distinctive features of the autoimmune disease.
Altered glutamate transmission is the core of parkinson's
https://www.google.com/search?q=glutamate+parkinson%27s&oq=glutamate+parki&aqs=chrome.0.0j69i57j0l4.5606j0j4&sourceid=chrome&ie=UTF-8
synuclein plaques are the hallmark of Parkinson's
How does synuclein connect to glutamate?
dermal skin nerve synucleins in those with REM sleep disorder Parkinsons
https://www.ncbi.nlm.nih.gov/pubmed/28180961
dermal skin nerve synucleins in those with Multiple system atrophy
https://www.ncbi.nlm.nih.gov/pubmed/26175301
even the gut of parkinson's patients has synuclein clumps!
http://www.livescience.com/36354-parkinsons-disease-colonoscopy-diagnosis.html
Hypothesis: The pathways of the receptor used by the virus causes the distinctive features of the autoimmune disease.
Altered glutamate transmission is the core of parkinson's
https://www.google.com/search?q=glutamate+parkinson%27s&oq=glutamate+parki&aqs=chrome.0.0j69i57j0l4.5606j0j4&sourceid=chrome&ie=UTF-8
synuclein plaques are the hallmark of Parkinson's
How does synuclein connect to glutamate?
alcohol and cocaine increase synuclein in brain
both cause increases in glutamate release
stimulation of the nerves by glutamate sends PARKIN to the mitochondria
PARKIN was discovered as the genetic mutation found in familia, genetic, parkinson's disease
HIGH glutamate or further down the path...over sensitive Parkin
Parkin causes the autophagy of mitochondrias (their destruction)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592826/
less functional nerves makes it look a lot like the death of nerves...which is the case for autoimmune parkinson's disease
less functional nerves makes it look a lot like the death of nerves...which is the case for autoimmune parkinson's disease
So does synucleins represent nerves stuck in secretion mode?
What causes this state of synucleins to precipitate and the neuron to be stuck secreting? A virus would typically have destroyed the cell making new viruses.
Parkinson's is an autoimmune disease where antibodies against synucleins have developed.
Autoimmune disease cross-targeting occurs when 2 infections exist on one target, one inside and one outside and self protection has broken down. (if you are attacking the outside and the inside there is no protection occurring)
All nerve cells with synuclein attacked?
dermal skin nerve synucleins in those with REM sleep disorder Parkinsons
https://www.ncbi.nlm.nih.gov/pubmed/28180961
dermal skin nerve synucleins in those with Multiple system atrophy
https://www.ncbi.nlm.nih.gov/pubmed/26175301
even the gut of parkinson's patients has synuclein clumps!
http://www.livescience.com/36354-parkinsons-disease-colonoscopy-diagnosis.html
mycobacteria in parkinson's and crohn's
https://www.ncbi.nlm.nih.gov/pubmed/?term=crohn%27s++synuclein
Guts of crohn's did not have synuclein until parkinson's developed
http://www.livescience.com/36354-parkinsons-disease-colonoscopy-diagnosis.html
which indicates this is not mycobacteria specific but rather when perhaps a virus shows up too.
However, neither alzheimers or chicken pox increase synuclein which might explain parkinsonism. The killing of nerves and not a specific focus on synuclein type.
Review with a focus on why these specific viruses: flu and flaviviruses
Synuclein is required for glutamate release (as linked before)
https://www.ncbi.nlm.nih.gov/pubmed/17689254
If syn which is involved with the vesicles and secretions of Glutamate by neurons is precipitating in parkinson's disease thus forming the signature synuclein plaques because the demand for glutamate has increased? more transport vesicles moving the glutamate....extra synuclein proteins...neurons stuck in secretion mode.
Is Parkinson's a state of over secretion of glutamate?
The amount of glutamate does appear to be increased in Parkinson's disease patients.
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030918
cAMP dependent Glutamate release
http://www.jbc.org/content/271/48/30554.full.pdf
D2 (dopamine receptor) activation inhibits cyclase activity (which converts ATP to cAMP)
D2 is used by the flu virus to enter the cell which would raise glutamate (stimulating the receptor as the virus entered)
Guts of crohn's did not have synuclein until parkinson's developed
http://www.livescience.com/36354-parkinsons-disease-colonoscopy-diagnosis.html
which indicates this is not mycobacteria specific but rather when perhaps a virus shows up too.
However, neither alzheimers or chicken pox increase synuclein which might explain parkinsonism. The killing of nerves and not a specific focus on synuclein type.
Review with a focus on why these specific viruses: flu and flaviviruses
Synuclein is required for glutamate release (as linked before)
https://www.ncbi.nlm.nih.gov/pubmed/17689254
If syn which is involved with the vesicles and secretions of Glutamate by neurons is precipitating in parkinson's disease thus forming the signature synuclein plaques because the demand for glutamate has increased? more transport vesicles moving the glutamate....extra synuclein proteins...neurons stuck in secretion mode.
Is Parkinson's a state of over secretion of glutamate?
The amount of glutamate does appear to be increased in Parkinson's disease patients.
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030918
cAMP dependent Glutamate release
http://www.jbc.org/content/271/48/30554.full.pdf
D2 (dopamine receptor) activation inhibits cyclase activity (which converts ATP to cAMP)
D2 is used by the flu virus to enter the cell which would raise glutamate (stimulating the receptor as the virus entered)
avian flu increases synuclein
flu viruses appear to use dopamine receptors
synuclein alters number of dopamine receptors
synuclein also appears with west nile virus infections
note that neuromelanin is now thought to cause synuclein
does secretion of melanin require synuclein?
neuromelanin accumulation and increased synuclein
west nile uses melanocortin receptor 3 (west nile infects the kidney too)
Parkinson's has been connect to two cancers: non hodgkin lymphoma and melanoma
Hepatitis C another flavivirus has also been linked to parkinson's
non hodgkin lymphoma and hep C
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