Finding points to possible mechanism underpinning Alzheimer's and Parkinson's diseases

http://medicalxpress.com/news/2015-0...-diseases.html

Life Extension Foundation sells the NAD+ precursor nicotinamide riboside and includes it with Life Extension Mix. Thorne also has it in a product called NiaCel.

More info at http://www.lef.org//Magazine/2014/11...Of-NAD/Page-01

Time for another experiment.

Here's another by Doctors Best http://www.drbvitamins.com/products/...ng-niagen-60vc

From Wiki:

"When bound to a protein, NAD+ and NADH are usually held within a structural motif known as the Rossmann fold.[38] The motif is named after Michael Rossmann who was the first scientist to notice how common this structure is within nucleotide-binding proteins.[39] This fold contains three or more parallel beta strands linked by two alpha helices in the order beta-alpha-beta-alpha-beta. This forms a beta sheet flanked by a layer of alpha helices on each side. Because each Rossmann fold binds one nucleotide, binding domains for NAD+ consist of two paired Rossmann folds, with each fold binding one of the two nucleotides of the cofactor.[39] However, this fold is not universal among NAD-dependent enzymes, since a class of bacterial enzymes involved in amino acid metabolism have recently been discovered that bind the coenzyme, but lack this motif.[40]"

I wonder if the mis-shaped alpha-synuclein folds in PD are really caused by lack of this critical B vitamin. Need to look into this further.

Analysis of the amino acid sequence of alpha-synuclein shows that it does not have a potential nucleotide-binding domain (a "Rossmann fold") so its putative ability to interact with NAD or other nucleotides seems unlikely to reflect its role in the pathology of Parkinson's Disease.

There is a review of current thinking about how misfolding of alpha-synuclein is linked to the pathology of Parkinson's Disease here: http://www.sciencedirect.com/science...25443911002250

J Neurol Sci. 2014 Dec 15;347(1-2):34-8. doi: 10.1016/j.jns.2014.10.024. Epub 2014 Oct 23.
A novel treatment target for Parkinson's disease.
Wakade C1, Chong R2.
Author information

Abstract
We hypothesize that GPR109A message and expression are up-regulated in individuals with Parkinson's disease (PD). GPR109A is a high-affinity niacin receptor. Niacin is a precursor for NAD-NADH which is needed for dopamine production. GPR109A and its agonists are known to exert anti-inflammatory actions in the skin, gut and retina. However these roles are neither anticipated nor established in the CNS. For the first time here we propose the roles of GPR109A and its agonists including niacin in CNS pathology. Moreover we predict that the neuroprotective roles of either niacin or butyrates in CNS occur via GPR109A.

http://www.ncbi.nlm.nih.gov/pubmed/25329911

Same lead author as in my previous posting ...

Dealing with niacin and NAD+ therapy for MS, PD and prion disease ...

Nicotinic acid said to be 200-fold more bioavailable than niacinamide.

[QUOTE=kukai8;1129723]Dealing with niacin and NAD+ therapy for MS, PD and prion disease

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What this MS-themed article actually states is: "In glia, nicotinic acid provides greater levels of NAD biosynthesis per mole than niacinamide or tryptophan, by 200- and 500-fold, respectively."

http://brain.oxfordjournals.org/content/138/4/992?rss=1

In vivo, toxic prion protein-induced degeneration of hippocampal neurons is prevented dose-dependently by intracerebral injection of NAD+. Intranasal NAD+ treatment of prion-infected sick mice significantly improves activity and delays motor impairment.