Could Nicotine be protective?

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
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Russ
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Could Nicotine be protective?

Post by Russ »

Here's one I don't think we've talked about before.... Robb Wolf shared an interesting 2014 article aggregating some provocative research on beneficial effects of nicotine, mostly anchored in Parkinson's....

http://discovermagazine.com/2014/march/13-nicotine-fix

...but sure enough, it does on to say...
And nicotine may have an antioxidant effect, serving to mop up the toxic free radicals produced as a byproduct of metabolism, thus protecting the brain. The neuroprotective effects of nicotine were studied in a randomized clinical trial involving 67 subjects in the early stages of Alzheimer’s disease, where memory was slightly impaired but decision-making and other cognitive abilities remained intact. They received either a 15-milligram nicotine patch or placebo for six months. The results found “significant nicotine-associated improvements in attention, memory and psychomotor speed,” with excellent safety and tolerability.
Thoughts?
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Schnooks
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Re: Could Nicotine be protective?

Post by Schnooks »

interesting.. although my aunt who smoke got alz. before she was 60 :(
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SusanJ
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Re: Could Nicotine be protective?

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I was intrigued by nicotine receptors when researching the vagus nerve. It can down regulate immune response in the body, so why not have effects in the brain?

Anti-Allergic Role of Cholinergic Neuronal Pathway via α7 Nicotinic ACh Receptors on Mucosal Mast Cells in a Murine Food Allergy Model (2014)
Vagal stimulation by 2-deoxy-D-glucose and drug treatment with nicotinic ACh receptor (nAChR) agonists (nicotine and α7 nAChR agonist GTS-21) alleviated the allergic symptoms in the FA mice. Nicotine treatment suppressed MMCs hyperplasia, enhanced MPO and upregulated mRNA expression of Th1 and Th2 cytokines in the FA mice colon. MMCs, which are negatively regulated by α7 nAChRs, were often located in close proximity to cholinergic CGRP-immunoreactive nerve fibers in the FA mice colon. The present results reveal that the cholinergic neuroimmune interaction via α7 nAChRs on MMCs is largely involved in maintaining intestinal immune homeostasis and can be a target for a new therapy against mucosal immune diseases with homeostatic disturbances such as FA.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894205/

Alpha7 nicotinic receptors as novel therapeutic targets for inflammation-based diseases (2013)
The expression and localization of alpha7 nicotinic receptors in synovial biopsies from patients with rheumatoid arthritis (RA) and psoriatic arthritis have been investigated [95]. Using alpha7-specific antibodies, alpha7-positive cells were detected mainly in synovial lining cells and vessels and were identified as primarily macrophages and fibroblasts, with the majority of these cells expressing the receptor. Alpha7 was also identified at both the mRNA and protein level in cultured fibroblast-like synoviocytes, and the alpha7 agonists nicotine and AR-R17779 reduced TNF-α, IL-6, and IL-8 production by synoviocytes. In other studies, acetylcholine significantly reduced the production of IL-6, the chemokines IL-8, CCL2, CCL3, CCL5, and GM-CSF by IL-1-stimulated synoviocytes, and these effects were blocked by the alpha7 antagonist MLA (methyllycaconitine) or by using alpha7 siRNA to knock down receptor expression [96]. The selective alpha7 agonist PNU-282987 also decreased the production of IL-6 by IL-1-stimulated synoviocytes.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678737/
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Re: Could Nicotine be protective?

Post by Harrison »

There has been a lot of work with nicotinic related drugs in Alzheimer's. Unfortunately every Phase III clinical trial so far has failed. There is an ongoing one for an alpha7 nicotinic agonist, reviewed here: https://www.ncbi.nlm.nih.gov/pubmed/25495510 and https://www.ncbi.nlm.nih.gov/pubmed/25438724

Interestingly, the drug Bredesen is testing in an Australian trial is known to activate alpha7 nicotinic receptors: https://www.ncbi.nlm.nih.gov/pubmed/25399811

I think the link of nicotine to helping Parkinson's patients is considered to be a lot stronger than the link of nicotine to help Alzheimer's patients.
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RichardS
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Re: Could Nicotine be protective?

Post by RichardS »

I am similarly skeptical of nicotine for AD. It was being investigated back in the late 80's when I started in neuropsychology. Nothing much has changes as best I can tell. Tacrine, the first approved drug for treatment of AD and cholinergic agonist (as is nicotine), had a minuscule if any clinical effect. I remember being amazed at the clinical trials that were the basis for its approval. Statistical mumbo-jumbo.

I have not looked at the Parkinson's research for a long time, but what I remember of it is that nicotine plays a special role unlikely to be found in AD. Parkinson's is primarily a defect of the dopaminergic neurons of the subtantia nigra that project to cholinergic (acetylcholine-rich) neurons of which nicotine is a primary form of acetylcholine. Curiously, smoking rates are notoriously low years or even decades before the onset of Parkinson's compared to those who do not go on to develop Parkinson's. I don't believe any such relationship exists with AD.

Perhaps there are some common immunological factors. I've not really looked into that, probably because my head starts to spin when it comes to a goodly portion of the immunology literature.
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