Attempting to connect amyloid to mitochondria movement (still writing)

Alzheimer's disease appears to be a dysfunction of the neurons's mitochondria.  The hallmark of Alzheimer's disease is the formation of amyloid plaques building up in the brain.  I had suggested previously that I thought the normal function of this amyloid protein was one of growth.  This post is a collection of links looking at what is currently known today and I am trying to piece together the mitochondria, amyloid, and this neuron growth notion into a feasible hypothesis that explains Alzheimer's.

First we know that agent orange, diacetyl (butter flavoring), and herpes which all damage the mitochondria cause amyloid plaque build up.

Diacetyl causes amyloid
http://www.ncbi.nlm.nih.gov/pubmed/22731744
Herpes causes amyloid
http://www.ncbi.nlm.nih.gov/pubmed/17980964
agent orange causes amyloid
http://www.publichealth.va.gov/exposures/agentorange/conditions/al_amyloidosis.asp

If you look at the full length protein before it is clipped it is found in the mitochondria and plasma membrane, specifically associated with calcium channels.

app in the mitochondria.
http://www.ncbi.nlm.nih.gov/pubmed/19544621
http://www.ncbi.nlm.nih.gov/pubmed/17911214
http://www.ncbi.nlm.nih.gov/pubmed/16943564

In alzheimer's you can see the app build up in the calcium channels

http://www.jneurosci.org/content/26/35/9057.full.pdf
Accumulation of Amyloid Precursor Protein in the Mitochondrial Import Channels of Human Alzheimer’s Disease Brain Is Associated with Mitochondrial Dysfunction

So here is what I am thinking: The app goes to the calcium channels, increases the calcium, turning up the mitochondria.  The mitochondria then moves down the nerve.  If you imagine the mitochondria as a little car that has to move down to where the nerve is growing or needing ATP at the tip of the nerve.

We already know that NO stops the mitochondria from moving
http://www.ncbi.nlm.nih.gov/pubmed/?term=mitochondria+moving+nitric

J Neurochem. 2006 May;97(3):724-36. Epub 2006 Apr 5.

Nitric oxide impairs mitochondrial movement in cortical neurons during hypoxia.

Zanelli SA1, Trimmer PA, Solenski NJ.

The mitochondria has it's own NO synthase.  

For fireflies NO turns off the mitochondria which turns off the fireflies light. 

NO turns the mito off....does Calcium turn it on? since muscles are driven by Calcium released from the ER it would be logical calcium might trigger the mitochondria too. 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1819417/
Aβ interacts directly with the Calcium channels and controls if and when the channels are at the membrane. Hypoxia increases Aβ . This is the L-type channel of the plasma membrane, what about the mitochondria's calcium channels, are they increased?

Is Aβ the calling card of the mitochondria asking it to move down the neuron? increase the calcium channels thus increasing the calcium thus increasing the ATP?

http://www.sciencedirect.com/science/article/pii/S000527280900036X

Mitochondrial calcium as a key regulator of mitochondrial ATP production in mammalian cells

• Elinor J. Griffiths^a, b, , , 
• Guy A. Rutter^c

The mitochondria's Calcium uniporter and app

http://www.ncbi.nlm.nih.gov/pubmed/23982146

FASEB J. 2013 Dec;27(12):4776-89. doi: 10.1096/fj.13-234765. Epub 2013 Aug 27.

Mitochondrial dysfunction and calcium deregulation by the RanBP9-cofilin pathway.

Roh SE1, Woo JA, Lakshmana MK, Uhlar C, Ankala V, Boggess T, Liu T, Hong YH, Mook-Jung I, Kim SJ, Kang DE.

• Abstract
J Mol Cell Cardiol. 2015 Jan;78:46-53. doi: 10.1016/j.yjmcc.2014.10.013. Epub 2014 Nov 4.

The mitochondrial calcium uniporter: mice can live and die without it.

Harrington JL1, Murphy E2

http://www.ncbi.nlm.nih.gov/pubmed/19544621

APP and myitochondrial dysfunction

Neurosci Lett. 2007 Dec 18;429(2-3):95-100. Epub 2007 Oct 13.

Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation.

Wozniak MA1, Itzhaki RF, Shipley SJ, Dobson CB.

BMC Microbiol. 2005 Aug 18;5:48.

Herpes simplex virus interferes with amyloid precursor protein processing.

Shipley SJ1, Parkin ET, Itzhaki RF, Dobson CB.

Sci Rep. 2015 Oct 21;5:15444. doi: 10.1038/srep15444.

Herpes Simplex Virus type-1 infection induces synaptic dysfunction in cultured cortical neurons via GSK-3 activation and intraneuronal amyloid-β protein accumulation.

Piacentini R1, Li Puma DD1, Ripoli C1, Elena Marcocci M2, De Chiara G3, Garaci E4, Teresa Palamara A2,4, Grassi C1,4.

Herpes viruses take over the mitochondrias transport and travel down the nerve.  Blocking calcium stopped the viral spread from one nerve to another

http://www.princeton.edu/main/news/archive/S33/79/51K43/

J Neurosci Res. 1991 Feb;28(2):192-9.

Nerve growth factor-induced increase in calcium uptake by PC12 cells.

Nikodijevic B1, Guroff G.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987503/

Lysine as a treatment for Alzheimer's because it helps herpes infections

J Neurochem. 1996 Jul;67(1):98-104.

Nerve growth factor and ras regulate beta-amyloid precursor protein gene expression in PC12 cells.

Cosgaya JM1, Latasa MJ, Pascual A.

http://www.ncbi.nlm.nih.gov/pubmed/26221415

Oxid Med Cell Longev. 2015;2015:787805. doi: 10.1155/2015/787805. Epub 2015 Jun 28.

Calcium Channel Blockers, Progression to Dementia, and Effects on Amyloid Beta Peptide Production.

Lovell MA1, Abner E2, Kryscio R3, Xu L4, Fister SX5, Lynn BC1.

amyloid beta treated (extra added to ) neurons have mitochondrias that don't move to the synapse and the synapse degrades

http://www.sciencedirect.com/science/article/pii/S0925443911000202


The genetics of Alzheimer's involves APOE.  (Allen Rose who discovered APOE believes the mitochondria is central to Alzheimer's)

I am trying to remember: omega fats  are in the inner mitochondrial membrane.  Vitamin E stabilizes the omega fats just as cholesterol does for the plasma membranes....APOE are fatty acid carriers. Does this fit with the mitochondrial hypothesis that the fluidity of the inner mitochondria is poor.  The mitochondrias do not function well? Imagine that you want more omega fats and you want it to be slick and fast. 

http://www.ncbi.nlm.nih.gov/pubmed/25333200

Nutrients. 2014 Oct 20;6(10):4452-71. doi: 10.3390/nu6104452.

Fatty acid metabolism in carriers of apolipoprotein E epsilon 4 allele: is it contributing to higher risk of cognitive decline and coronary heart disease?

Chouinard-Watkins R1, Plourde M2.