On Saturday, March 10, 2012 at 6:15:21 PM UTC-6, Kofi wrote:
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.
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