2012-03-11 00:15:21 UTC
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
Palada V, et al. Show all
Palada V, TerzicŽ J, Mazzulli J, Bwala G, Hagenah J, Peterlin B, Hung
AY, Klein C, Krainc D.
Neurobiol Aging. 2012 Apr;33(4):836.e1-3. Epub 2011 Jul 27.
Mediterranean Institute for Life Science, Split, Croatia.
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 Â© 2012 Elsevier Inc. All rights reserved.
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