The role of histamine release in Parkinson's

[Kofi]

I hate PubMed mobile. Every 'upgrade' has made the text-based version
of Pubmed less useful.

Anyway - unless I'm misreading this - Parkinson's patients are less
likely to have a low activity histamine-metabolizing enzyme (which would
elevate histamine levels). This means histamine may be a protective
factor against Parkinson's. However, I'm not sure what the authors mean
by "lower HNMT activity plays a role in the pathogenesis of PD" and
there's evidence that IgG's interact with receptors on neurons to
trigger Parkinson's degeneration. I had thought mast cell degranulation
would have just the opposite effect on Parkinson's risk. Perhaps I'm
missing some sort of histamine-cholinergic interaction.

Can someone with access to the paper indicate whether my interpretation
is consistent with the actual conclusions of the authors?



Histamine N-methyltransferase Thr105Ile polymorphism is associated with
Parkinson's disease.

Authors
Palada V, et al. Show all
Palada V, TerzicŽ J, Mazzulli J, Bwala G, Hagenah J, Peterlin B, Hung
AY, Klein C, Krainc D.

Journal

Neurobiol Aging. 2012 Apr;33(4):836.e1-3. Epub 2011 Jul 27.

Affiliation

Mediterranean Institute for Life Science, Split, Croatia.

Abstract

Histamine is a central neurotransmitter degraded by
histamine-N-methyltransferase (HNMT). Several abnormalities in the
histaminergic system were found in patients with Parkinson's disease
(PD), thus we tested the possible association of a Thr105Ile functional
polymorphism in HNMT with PD. A total of 913 patients with PD and 958
controls were genotyped using a TaqMan RT-PCR Genotyping Assay (Foster
City, California, USA). Lower frequency of HNMT Ile105 allele that is
associated with decreased enzymatic activity was found in patients
compared with controls (c(2) = 11.65; p = 0.0006). We performed
meta-analysis to confirm the association of Thr105Ile functional
polymorphism with PD. Our results indicate that lower HNMT activity
plays a role in the pathogenesis of PD.
Copyright © 2012 Elsevier Inc. All rights reserved.

PMID 21794955


the Fc receptor of IgG (FcRgamma) contributes to neuronal death in
ischemic injury and Parkinson's disease; FcRgamma knockout stops
hippocampal pyramidal cell death induced by kainic acid (KA);
FcgammaRIIB protein occured in parvalbumin neurons (interneurons?),
whereas FcgammaRIII and FcgammaRI proteins were detected in microglial
cells; knockout blocked microglial activation, nitrotyrosine production
and iNOS/COX-2 and also tissue plasminogen activator (tPA); neutralizing
antibodies against FcgammaRll and FcgammaRlll had the same protective
affect. In addition, the neutralizing antibody reduced oxidative stress
and expression of proteases [PMID 20074624]

FcgammaRIIB is the preferential receptor for
allergy/autimmunity-blocking IgG4 [PMID 19018092] (IgG4 is elevated by
helminth infection and IL-10)

parvalbumin is a calcium-binding albumin protein, localized in
fast-twitch muscle and in the brain and some endocrine tissue; it
organizes microtubules, calcium signaling cell-cycle regulation and
second messenger production; Parvalbumin occurs in gabaergic
interneurons and is an allergen causing the major (fish) seafood allergy

[Olafur Pall Olafsson]

I hate PubMed mobile.  Every 'upgrade' has made the text-based version
of Pubmed less useful.
Anyway - unless I'm misreading this - Parkinson's patients are less
likely to have a low activity histamine-metabolizing enzyme (which would
elevate histamine levels).  This means histamine may be a protective
factor against Parkinson's.  However, I'm not sure what the authors mean
by "lower HNMT activity plays a role in the pathogenesis of PD" and
there's evidence that IgG's interact with receptors on neurons to
trigger Parkinson's degeneration.  I had thought mast cell degranulation
would have just the opposite effect on Parkinson's risk.  Perhaps I'm
missing some sort of histamine-cholinergic interaction.
Can someone with access to the paper indicate whether my interpretation
is consistent with the actual conclusions of the authors?
Histamine N-methyltransferase Thr105Ile polymorphism is associated with
Parkinson's disease.
Authors
Palada V, et al. Show all
Palada V, Terzic´ J, Mazzulli J, Bwala G, Hagenah J, Peterlin B, Hung
AY, Klein C, Krainc D.
Journal
Neurobiol Aging. 2012 Apr;33(4):836.e1-3. Epub 2011 Jul 27.
Affiliation
Mediterranean Institute for Life Science, Split, Croatia.
Abstract
Histamine is a central neurotransmitter degraded by
histamine-N-methyltransferase (HNMT). Several abnormalities in the
histaminergic system were found in patients with Parkinson's disease
(PD), thus we tested the possible association of a Thr105Ile functional
polymorphism in HNMT with PD. A total of 913 patients with PD and 958
controls were genotyped using a TaqMan RT-PCR Genotyping Assay (Foster
City, California, USA). Lower frequency of HNMT Ile105 allele that is
associated with decreased enzymatic activity was found in patients
compared with controls (c(2) = 11.65; p = 0.0006). We performed
meta-analysis to confirm the association of Thr105Ile functional
polymorphism with PD. Our results indicate that lower HNMT activity
plays a role in the pathogenesis of PD.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID 21794955

Hi Kofi,

The abstract is a bit misleading. In short, there are two alleles:
Thr105 and Ile105. Thr105 is the common allele while the lle105 refers
to a polymorphic substitution where threonine has been replaced by
isoleucine. According to the full text, individuals heterozygous for
Ile105 allele have 30% to 50% lower HNMT activity. It is clear from
the full text that lower frequency of the IIe105 allele is found in PD
patients compared to controls. From this information your statement
that histamine may be a protective factor against PD would be
correct.

You make a good point in that the last statement of the abstract
(lower HNMT activity plays a role in the pathogenesis of PD) appears
to contradict this. I think it does. The last sentence of the full
text states this:

"Because Ile105 allele leads to lower activity of the enzyme our
finding suggests that lower HNMT activity contributes to the
pathogenesis of PD. It would be therefore of interest to further
examine the neurophysiological consequences of the HNMT Thr105Ile
polymorphism."

This sentence is plain wrong, or misleading at best, If I am reading
the full text correctly. They should have said something like "higher
HNMT activity contributes to the pathogenesis of PD" or "lower HNMT
activity plays a role in PD" since Table 1 in the full text makes it
pretty clear that the low activity lle105 allele is found at a lower
frequency in PD patients compared to controls.

[m***@gmail.com]

Post by Kofi
I hate PubMed mobile. Every 'upgrade' has made the text-based version
of Pubmed less useful.
Anyway - unless I'm misreading this - Parkinson's patients are less
likely to have a low activity histamine-metabolizing enzyme (which would
elevate histamine levels). This means histamine may be a protective
factor against Parkinson's. However, I'm not sure what the authors mean
by "lower HNMT activity plays a role in the pathogenesis of PD" and
there's evidence that IgG's interact with receptors on neurons to
trigger Parkinson's degeneration. I had thought mast cell degranulation
would have just the opposite effect on Parkinson's risk. Perhaps I'm
missing some sort of histamine-cholinergic interaction.
Can someone with access to the paper indicate whether my interpretation
is consistent with the actual conclusions of the authors?
Histamine N-methyltransferase Thr105Ile polymorphism is associated with
Parkinson's disease.
Authors
Palada V, et al. Show all
Palada V, Terzic´ J, Mazzulli J, Bwala G, Hagenah J, Peterlin B, Hung
AY, Klein C, Krainc D.
Journal
Neurobiol Aging. 2012 Apr;33(4):836.e1-3. Epub 2011 Jul 27.
Affiliation
Mediterranean Institute for Life Science, Split, Croatia.
Abstract
Histamine is a central neurotransmitter degraded by
histamine-N-methyltransferase (HNMT). Several abnormalities in the
histaminergic system were found in patients with Parkinson's disease
(PD), thus we tested the possible association of a Thr105Ile functional
polymorphism in HNMT with PD. A total of 913 patients with PD and 958
controls were genotyped using a TaqMan RT-PCR Genotyping Assay (Foster
City, California, USA). Lower frequency of HNMT Ile105 allele that is
associated with decreased enzymatic activity was found in patients
compared with controls (c(2) = 11.65; p = 0.0006). We performed
meta-analysis to confirm the association of Thr105Ile functional
polymorphism with PD. Our results indicate that lower HNMT activity
plays a role in the pathogenesis of PD.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID 21794955
the Fc receptor of IgG (FcRgamma) contributes to neuronal death in
ischemic injury and Parkinson's disease; FcRgamma knockout stops
hippocampal pyramidal cell death induced by kainic acid (KA);
FcgammaRIIB protein occured in parvalbumin neurons (interneurons?),
whereas FcgammaRIII and FcgammaRI proteins were detected in microglial
cells; knockout blocked microglial activation, nitrotyrosine production
and iNOS/COX-2 and also tissue plasminogen activator (tPA); neutralizing
antibodies against FcgammaRll and FcgammaRlll had the same protective
affect. In addition, the neutralizing antibody reduced oxidative stress
and expression of proteases [PMID 20074624]
FcgammaRIIB is the preferential receptor for
allergy/autimmunity-blocking IgG4 [PMID 19018092] (IgG4 is elevated by
helminth infection and IL-10)
parvalbumin is a calcium-binding albumin protein, localized in
fast-twitch muscle and in the brain and some endocrine tissue; it
organizes microtubules, calcium signaling cell-cycle regulation and
second messenger production; Parvalbumin occurs in gabaergic
interneurons and is an allergen causing the major (fish) seafood allergy

[m***@gmail.com]

Post by Kofi
I hate PubMed mobile. Every 'upgrade' has made the text-based version
of Pubmed less useful.
Anyway - unless I'm misreading this - Parkinson's patients are less
likely to have a low activity histamine-metabolizing enzyme (which would
elevate histamine levels). This means histamine may be a protective
factor against Parkinson's. However, I'm not sure what the authors mean
by "lower HNMT activity plays a role in the pathogenesis of PD" and
there's evidence that IgG's interact with receptors on neurons to
trigger Parkinson's degeneration. I had thought mast cell degranulation
would have just the opposite effect on Parkinson's risk. Perhaps I'm
missing some sort of histamine-cholinergic interaction.
Can someone with access to the paper indicate whether my interpretation
is consistent with the actual conclusions of the authors?
Histamine N-methyltransferase Thr105Ile polymorphism is associated with
Parkinson's disease.
Authors
Palada V, et al. Show all
Palada V, Terzic´ J, Mazzulli J, Bwala G, Hagenah J, Peterlin B, Hung
AY, Klein C, Krainc D.
Journal
Neurobiol Aging. 2012 Apr;33(4):836.e1-3. Epub 2011 Jul 27.
Affiliation
Mediterranean Institute for Life Science, Split, Croatia.
Abstract
Histamine is a central neurotransmitter degraded by
histamine-N-methyltransferase (HNMT). Several abnormalities in the
histaminergic system were found in patients with Parkinson's disease
(PD), thus we tested the possible association of a Thr105Ile functional
polymorphism in HNMT with PD. A total of 913 patients with PD and 958
controls were genotyped using a TaqMan RT-PCR Genotyping Assay (Foster
City, California, USA). Lower frequency of HNMT Ile105 allele that is
associated with decreased enzymatic activity was found in patients
compared with controls (c(2) = 11.65; p = 0.0006). We performed
meta-analysis to confirm the association of Thr105Ile functional
polymorphism with PD. Our results indicate that lower HNMT activity
plays a role in the pathogenesis of PD.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID 21794955
the Fc receptor of IgG (FcRgamma) contributes to neuronal death in
ischemic injury and Parkinson's disease; FcRgamma knockout stops
hippocampal pyramidal cell death induced by kainic acid (KA);
FcgammaRIIB protein occured in parvalbumin neurons (interneurons?),
whereas FcgammaRIII and FcgammaRI proteins were detected in microglial
cells; knockout blocked microglial activation, nitrotyrosine production
and iNOS/COX-2 and also tissue plasminogen activator (tPA); neutralizing
antibodies against FcgammaRll and FcgammaRlll had the same protective
affect. In addition, the neutralizing antibody reduced oxidative stress
and expression of proteases [PMID 20074624]
FcgammaRIIB is the preferential receptor for
allergy/autimmunity-blocking IgG4 [PMID 19018092] (IgG4 is elevated by
helminth infection and IL-10)
parvalbumin is a calcium-binding albumin protein, localized in
fast-twitch muscle and in the brain and some endocrine tissue; it
organizes microtubules, calcium signaling cell-cycle regulation and
second messenger production; Parvalbumin occurs in gabaergic
interneurons and is an allergen causing the major (fish) seafood allergy

[m***@gmail.com]

Post by Kofi
I hate PubMed mobile. Every 'upgrade' has made the text-based version
of Pubmed less useful.
Anyway - unless I'm misreading this - Parkinson's patients are less
likely to have a low activity histamine-metabolizing enzyme (which would
elevate histamine levels). This means histamine may be a protective
factor against Parkinson's. However, I'm not sure what the authors mean
by "lower HNMT activity plays a role in the pathogenesis of PD" and
there's evidence that IgG's interact with receptors on neurons to
trigger Parkinson's degeneration. I had thought mast cell degranulation
would have just the opposite effect on Parkinson's risk. Perhaps I'm
missing some sort of histamine-cholinergic interaction.
Can someone with access to the paper indicate whether my interpretation
is consistent with the actual conclusions of the authors?
Histamine N-methyltransferase Thr105Ile polymorphism is associated with
Parkinson's disease.
Authors
Palada V, et al. Show all
Palada V, Terzic´ J, Mazzulli J, Bwala G, Hagenah J, Peterlin B, Hung
AY, Klein C, Krainc D.
Journal
Neurobiol Aging. 2012 Apr;33(4):836.e1-3. Epub 2011 Jul 27.
Affiliation
Mediterranean Institute for Life Science, Split, Croatia.
Abstract
Histamine is a central neurotransmitter degraded by
histamine-N-methyltransferase (HNMT). Several abnormalities in the
histaminergic system were found in patients with Parkinson's disease
(PD), thus we tested the possible association of a Thr105Ile functional
polymorphism in HNMT with PD. A total of 913 patients with PD and 958
controls were genotyped using a TaqMan RT-PCR Genotyping Assay (Foster
City, California, USA). Lower frequency of HNMT Ile105 allele that is
associated with decreased enzymatic activity was found in patients
compared with controls (c(2) = 11.65; p = 0.0006). We performed
meta-analysis to confirm the association of Thr105Ile functional
polymorphism with PD. Our results indicate that lower HNMT activity
plays a role in the pathogenesis of PD.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID 21794955
the Fc receptor of IgG (FcRgamma) contributes to neuronal death in
ischemic injury and Parkinson's disease; FcRgamma knockout stops
hippocampal pyramidal cell death induced by kainic acid (KA);
FcgammaRIIB protein occured in parvalbumin neurons (interneurons?),
whereas FcgammaRIII and FcgammaRI proteins were detected in microglial
cells; knockout blocked microglial activation, nitrotyrosine production
and iNOS/COX-2 and also tissue plasminogen activator (tPA); neutralizing
antibodies against FcgammaRll and FcgammaRlll had the same protective
affect. In addition, the neutralizing antibody reduced oxidative stress
and expression of proteases [PMID 20074624]
FcgammaRIIB is the preferential receptor for
allergy/autimmunity-blocking IgG4 [PMID 19018092] (IgG4 is elevated by
helminth infection and IL-10)
parvalbumin is a calcium-binding albumin protein, localized in
fast-twitch muscle and in the brain and some endocrine tissue; it
organizes microtubules, calcium signaling cell-cycle regulation and
second messenger production; Parvalbumin occurs in gabaergic
interneurons and is an allergen causing the major (fish) seafood allergy

I'VE BEEN READING about elevated/low histamine levels in PD. In general, elevated desired levels are thwarted by slow/low thyroid and low-dose Naltrexone is suggested.