<center><a href="https://commons.wikimedia.org/wiki/File:Icelandic_sheep_summer_06.jpg" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmPvyG3FpZryv9biGu3HRBDzwx2bt13XsLgozXW1T4rXiU/Icelandic2_sheep_summer_06%20biologyfishman%202.0%20generic.jpg" alt="Icelandic2_sheep_summer_06 biologyfishman 2.0 generic.jpg"></a></center>
<hr>
<p>A few weeks ago I wrote a blog, <a href="https://steemit.com/letsmakeacollage/@agmoore/the-genius-of-sheep-lmac-12">"The Genius of Sheep".</a> I learned that not only are sheep very smart, but they also may hold promise of a treatment for <a href="https://www.theguardian.com/science/2017/jul/08/medical-research-transgenic-sheep-huntingtons-disease" rel="noopener" title="This link will take you away from steemit.com">Huntington's  Disease.</a>
 Huntington's is a particularly cruel disease because its victims know 
what their fate will be. They will likely have watched a grandfather, 
mother, uncle or sister decline and die from the illness.</p>
<p>I was both interested to find out more about this sheep substance and
 was also skeptical of the claims for its curative powers.  There's 
money to be made from raising the sheep and from extracting and 
marketing the substance.</p>
<p>However, I didn't understand the pathology of Huntington's, or 
neurodegenerative diseases in general.  If I was going to write a 
blog--and that did become my ambition--a lot of work lay ahead.  After 
doing that work,  I learned one thing for certain: there is a profound 
gulf between what scientists know about neurodegenerative diseases and 
what they need to know in order to significantly help patients.  
Effective treatment, and even a cure, resides in bridging that gulf.</p>
<hr>
<hr>
<center><a href="https://commons.wikimedia.org/wiki/File:Woody_Guthrie_2.jpg" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmVrwHwzrNQuYqK8YcYrGhLa6cHyWVaLCPu1phedf8dUMS/Woody%20Guthrie2%20World%20Telegraph%20photo%20at%20Library%20of%20congress%20public.jpg" alt="Woody Guthrie2 World Telegraph photo at Library of congress public.jpg"></a></center>
<blockquote>
<p><em>I think the first person who brought the tragedy of Huntington's 
Disease home for me was Woody Guthrie. Guthrie was a folk singer and 
political activist who battled Huntington's for the last years of his 
life.  He died in 1967. Two of his children died of the disease, and his
 father did also.</em></p>
</blockquote>
<hr>
<h4><center>GM1 Ganglioside</center></h4>
<hr>
<p>My quest for understanding the mechanics of Huntington's and other 
neurodegenerative diseases began with research into the mysterious sheep
 substance, GM1 ganglioside. This substance is found not only in sheep, 
but also on <a href="https://academic.oup.com/glycob/article/17/1/1R/715963" rel="noopener" title="This link will take you away from steemit.com">cell membranes</a> of all animals.  GM1 performs many <a href="https://link.springer.com/chapter/10.1007/978-1-4684-1200-0_28" rel="noopener" title="This link will take you away from steemit.com">functions</a> throughout the body, but plays an especially important role in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972652/" rel="noopener" title="This link will take you away from steemit.com">signalling:</a> it helps nerve cells (neurons) to communicate with each other, to receive and transmit messages.</p>
<hr>
<h6><center>A Critical Balance</center></h6>
<hr>
<p>Nature, it turns out, is whimsical in its distribution of GM1 ganglioside. Some people have <a href="https://rarediseases.info.nih.gov/diseases/10891/gm1-gangliosidosis" rel="noopener" title="This link will take you away from steemit.com">too much--</a>-- that's called gangliosidosis--and some people have too little.</p>
<p>Among the people who have too little are those afflicted with <a href="https://www.ncbi.nlm.nih.gov/pubmed/29747823" rel="noopener" title="This link will take you away from steemit.com">Parkinson's</a>and <a href="https://www.hdinhd.org/feed-items/disease-modifying-effects-of-ganglioside-gm1-in-huntingtons-disease-models/" rel="noopener" title="This link will take you away from steemit.com">Huntington's.</a>
   This is where sheep come into the picture, because some of them have 
gangliosidosis-- way too much GM1 ganglioside.  This is a genetic 
affliction.  By manipulating the genes of sheep--creating transgenic 
sheep--scientists are able to produce whole flocks that have 
gangliosidosis.</p>
<p><a href="http://embomolmed.embopress.org/content/early/2017/10/09/emmm.201707763" rel="noopener" title="This link will take you away from steemit.com">Trials were conducted</a>
 in which mice suffering from Huntington's were given ovine--sheep-- GM1
 ganglioside (directly into the brain).  These mice showed significant 
improvement. There have also been <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532888/" rel="noopener" title="This link will take you away from steemit.com">trials</a>
 that tested the effectiveness of GM1 ganglioside on symptoms of 
Parkinson's disease.  This research used human subjects.  
Bovine--cow--ganglioside was used.  The results of these trials showed 
that GM1 did ameliorate symptoms of Parkinson's.</p>
<p>Bovine <a href="http://www.glycoscienceresearch.com/exec-summary/" rel="noopener" title="This link will take you away from steemit.com">GM1 is no longer used</a>
 because of mad cow disease (the material is harvested from brains). If 
GM1 is to be used therapeutically, it will have to come from sheep.</p>
<hr>
<h5><center>Tay-Sachs Disease:  A Hereditary Gangliosidosis in Humans</center></h5>
<center><a href="https://commons.wikimedia.org/wiki/File:Tay-sachsUMich.jpg" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmTT6314Zx4qBA7EevFtBetsRMiTrH3bp1PLv7B7jAZPAQ/Tay-sachsUMich%20Jonathan%20Trobe,%20M.D.%203.0.jpg" alt="Tay-sachsUMich Jonathan Trobe, M.D. 3.0.jpg"></a></center>
<blockquote>
<p><em><a href="https://www.ncbi.nlm.nih.gov/pubmed/19820796" rel="noopener" title="This link will take you away from steemit.com">Tay-Sachs</a>
 is  an autosomal recessive disease, which means a child has to inherit 
two copies of the gene to be affected. Hallmark cherry-red spots may be 
evident the eyes of those afflicted.  Children usually do not survive 
past early childhood.</em></p>
</blockquote>
<hr>
<hr>
<hr>
<hr>
<h5><center>GM1 Ganglioside and Alzheimer's</center></h5>
<hr>
<p>It's important to note that what may be therapeutic for one 
neurodegenerative disease may have the reverse effect in another.  An 
illustration of this:  recent research indicates that GM1 ganglioside 
may actually accelerate the development of Alzheimer's disease.  The 
destructive beta-amyloid protein (hallmark of Alzheimer's) <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974419/" rel="noopener" title="This link will take you away from steemit.com">binds to GM1 ganglioside</a> in the brains of <em>Drosophila</em>--the fruit fly.  The is significant for people because it turns out that the <a href="https://www.technologynetworks.com/neuroscience/articles/unlocking-the-secrets-of-brain-organization-in-the-fruit-fly-310488" rel="noopener" title="This link will take you away from steemit.com">neural connectivity of a fruit fly</a>
 is remarkably similar to a human's.  So research on the fruit fly 
brain, it is believed, offers good insight into how human neuron 
messaging works.  If beta-amyloid binds to GM1 in a fruit fly's brain, 
it may show the same inclination in humans.</p>
<hr>
<h5><center>Fruit Fly</center></h5>
<center><a href="https://commons.wikimedia.org/wiki/File:Drosophila_melanogaster_-_side_(aka).jpg" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmfQ9NoxoBmNGZC7DnpRC4m3ntRGGoxuoYPHtYe4ipkkvN/Drosophila%202%20melanogaster_-_side_Andr%C3%A9%20Karwath%20aka%20Aka%202.5.jpg" alt="Drosophila 2 melanogaster_-_side_André Karwath aka Aka 2.5.jpg"></a></center>
<hr>
<p>So GM1ganglioside may help alleviate symptoms of Parkinson's and may 
accelerate the progress of Alzheimer's.  We know that it alleviates 
symptoms of Huntington's. How?  I pulled up an article that described 
the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793032/" rel="noopener" title="This link will take you away from steemit.com">neutralizing effect</a>
 of GM1 on the disease causing-agent in Huntington's, a protein called 
mutant Huntingtin (mHTT). According to the article, in studies on 
transgenic mice (bred to have the disease) infusion of GM1 into the 
brain <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793032/" rel="noopener" title="This link will take you away from steemit.com">weakened the toxic effects</a> of mHTT.  Treated mice demonstrated normal motor function.</p>
<hr>
<h4><center>Transgenic Mice with Huntington's</center></h4>
<center><a href="https://commons.wikimedia.org/w/index.php?title=File%3AResponses-to-Environmental-Enrichment-Differ-with-Sex-and-Genotype-in-a-Transgenic-Mouse-Model-of-pone.0009077.s002.ogv" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmWehc3mcdym41zRt84xE47cmzyL9k2BsWDaNSeUE3oGgz/mice2%20in%20playground%204.0%20hunington's.jpg" alt="mice2 in playground 4.0 hunington's.jpg"></a></center>
<blockquote>
<p><em>These mice were bred with the mutant HTT gene.  They are part of 
an experiment to see if environment can influence the progress of the 
disease. This <a href="https://upload.wikimedia.org/wikipedia/commons/8/81/Responses-to-Environmental-Enrichment-Differ-with-Sex-and-Genotype-in-a-Transgenic-Mouse-Model-of-pone.0009077.s002.ogv" rel="noopener" title="This link will take you away from steemit.com">video</a> shows the mice interacting in what is described as their playground.</em></p>
</blockquote>
<hr>
<hr>
<hr>
<p>Where does all of this information leave researchers?  It leaves them
 with a lot of unanswered questions.  It's obvious that GM1 ganglioside 
has great potential as a subject of research.  Will that research lead 
to understanding neurodegenerative disease? Will it lead to treatments, 
or cures? Some people think so. At the moment <a href="https://youtube" rel="noopener" title="This link will take you away from steemit.com">transgenic sheep</a>
 (sheep bred with the gene to develop gangliosidosis) are being raised 
with the hope that they will be part of a treatment plan for 
Huntington's and Parkinson's diseases.</p>
<hr>
<hr>
<h1><center>Neurodegenerative Diseases</center></h1>
<hr>
<p>Neuroconnectivity: it is the basis of the communication network that keeps our bodies functioning.</p>
<hr>
<h4><center>A Ballet in Which One Misstep Brings Disaster</center></h4>
<center><a href="https://commons.wikimedia.org/wiki/File:SynapseSchematic_en.svg" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmRd3kFdDGHuD5mGJnjoWmHzBBmGV1QqtFKRH6g43HMADH/Synapse%20Schematic%20Thomas%20Splettstoesser%20(www.scistyle.com)%20CC%204.0.jpg" alt="Synapse Schematic Thomas Splettstoesser (www.scistyle.com) CC 4.0.jpg"></a></center>
<blockquote>
<p><em>As I look at this diagram, I am struck by how ordered it seems.  
The role of each part of the synapse is so clear.  And then my eye 
catches one piece,"Voltage Gated Ca2+ Channel". This is such a small 
part, so easy to overlook.  And yet, this one piece once held the key to
 my brother's future.  A few years ago, a mysterious encephalitis 
suddenly overcame him. It defied diagnosis.   He had seizures, dementia,
 movement disruption.  Then a brilliant doctor put the bits of the 
diagnostic puzzle together and concluded that my brother had <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140680/" rel="noopener" title="This link will take you away from steemit.com">autoimmune voltage-gated encephalitis.</a>
  A tiny piece of the synapse, shown in the illustration, was being 
attacked by my brother's own immune system.  Massive doses of immune 
suppressive drugs, and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381605/" rel="noopener" title="This link will take you away from steemit.com">plasmapheresis,</a> stopped the attack.</em></p>
</blockquote>
<hr>
<h4><center>The Synapse</center></h4>
<hr>
<p>The basic function of a neuron is to transmit information.  The 
transmission of information between neurons occurs across a tiny space, a
 synapse.  This transmission is dependent upon a host of factors, 
including neurotransmitters, which are like chemical railways.  They 
carry information from one neuron to another.</p>
<p>In 2016 a group of neuroscientists got together to consider 
disturbances in synapses as a unifying characteristic of neurological 
disorders. The featured topic at the 2016 symposium was  <a href="https://www.scholars.northwestern.edu/en/publications/synaptopathies-synaptic-dysfunction-in-neurological-disorders-a-r" rel="noopener" title="This link will take you away from steemit.com">Synaptopathies: synaptic dysfunction in neurological disorders.</a>
   A report came out of the conference.  This suggested that a clue to 
causes, treatments and cures for many diseases of the brain might be 
found in studying synapse disturbance.  The conferees were not only 
addressing neurodegenerative diseases, but also other conditions such as
 Downs Syndrome, autism and epilepsy.</p>
<hr>
<h5><center>Neurodegenerative</center></h5>
<p>Three neurodegenerative diseases already mentioned in this 
post--Alzheimer's, Huntington's and Parkinson's--are often compared with
 one another (by neurologists).  It is thought that in understanding the
 process that leads to illness in each of the three, an understanding of
 the underlying disease processes for all may emerge.</p>
<hr>
<center><a href="https://commons.wikimedia.org/wiki/File:Positron_Emission_Tomography_(PET)_images_from_a_Parkinson%27s_patient_before_and_after_fetal_tissue_transplantation..jpg" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmZYYRSgELkq2vDwADQM38gp8DAdEedmHXA4Pwb5xzPxE1/PET%20scan%20of%20parkinsons%20patient%20after%20fetal%20tissue%20NIH%20public.jpg" alt="PET scan of parkinsons patient after fetal tissue NIH public.jpg"></a></center>
<blockquote>
<p><em>In Parkinson's Disease there's a disruption in dopamine delivery 
because dopamine receptors are destroyed.  One therapeutic approach is 
to implant fetal tissue in the brain of a patient.  In these before and 
after images, you can see that there is an increase in dopamine uptake a
 year after the surgery.</em></p>
</blockquote>
<hr>
<hr>
<hr>
<h5><center>Amyloid Proteins</center></h5>
<hr>
<p>A recent study (2017) discovered a significant similarity between the
 way these three neurological diseases spread through the brain  (and 
also <a href="https://concussionfoundation.org/CTE-resources/what-is-CTE" rel="noopener" title="This link will take you away from steemit.com">chronic traumatic encephalopathy--</a> injury from sports concussions).  In each case there seems to be a <a href="https://ecommons.luc.edu/luc_diss/2586/" rel="noopener" title="This link will take you away from steemit.com">rupture within a cell</a> that has encircled a pathogenic protein. The <a href="https://n.neurology.org/content/91/23_Supplement_1/S26.3" rel="noopener" title="This link will take you away from steemit.com">rupture results in dispersal</a> of the disruptive protein.   In the case of Parkinson's the protein is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281589/" rel="noopener" title="This link will take you away from steemit.com">α-Synuclein</a>, in Huntington's it's <a href="https://www.cell.com/molecular-cell/pdf/S1097-2765(18)30277-6.pdf" rel="noopener" title="This link will take you away from steemit.com">polyglutamine-expanded huntingtin</a>, and in Alzheimer's it's <a href="https://medicalxpress.com/news/2018-07-big-alzheimer-scientists-id-genesis.html" rel="noopener" title="This link will take you away from steemit.com">β-amyloid and tau.</a></p>
<hr>
<hr>
<center><a href="https://commons.wikimedia.org/wiki/File:Neuron_with_mHtt_inclusion.jpg" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmWmLvZ9d4Qfh7cLDLTLZDDovJ4C15r2hDD3Fqwz8c4EgA/Huntingtins%20inclusion.jpg" alt="Huntingtins inclusion.jpg"></a></center>
<blockquote>
<p><em>This is a montage of three images showing neurons affected by the
 mutant HTT protein.   The yellow orb with tendrils is an affected 
neuron.  The orange blob in the middle of that orb represents huntingtin
 proteins (HTT) collecting together abnormally in an <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873140/" rel="noopener" title="This link will take you away from steemit.com">inclusion.</a></em></p>
</blockquote>
<p>One result of this blossoming protein field is plaque formation, or 
protein clumping.  Although many of us have heard that plaques are a 
diagnostic feature of <a href="https://www.brightfocus.org/alzheimers-disease/infographic/amyloid-plaques-and-neurofibrillary-tangles" rel="noopener" title="This link will take you away from steemit.com">Alzheimer's,</a> these plaques are also present in <a href="https://www.sciencedaily.com/releases/2016/02/160203134848.htm" rel="noopener" title="This link will take you away from steemit.com">Huntington's</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478091/" rel="noopener" title="This link will take you away from steemit.com">Parkinson's.</a></p>
<p>In Huntington's the aggregation of proteins in the brain is referred to as <a href="https://www.sciencedaily.com/releases/2016/02/160203134848.htm" rel="noopener" title="This link will take you away from steemit.com">"clumping".</a></p>
<p>A factor the three disease have in common is cell death.  In each of the three diseases a <a href="https://www.ncbi.nlm.nih.gov/pubmed/16722804" rel="noopener" title="This link will take you away from steemit.com">misfolding protein</a> has been identified as instigating cell death. A 2013 article in <a href="https://www.frontiersin.org/articles/10.3389/fmolb.2019.00020/full" rel="noopener" title="This link will take you away from steemit.com">"Frontiers in Molecular Biosciences"</a>
 states, "...there is increasing evidence that in general, smaller 
soluble toxic misfolded oligomers are the main causative agent for 
neurodegeneration."<sup><a href="https://steemit.com/submit.html#footnote1" rel="noopener" title="This link will take you away from steemit.com">1</a></sup></p>
<hr>
<hr>
<h2><center>Glutamate: An Essential Neurotransmitter</center></h2>
<hr>
<h5><center>Glutamate: Not Enough in Huntington's. Too Much in Parkinson's and Alzheimer's</center></h5>
<hr>
<p>Glutamate is a vital neurotransmitter.  We need it in our synapses—<a href="https://thebrain.mcgill.ca/flash/i/i_01/i_01_m/i_01_m_ana/i_01_m_ana.html" rel="noopener" title="This link will take you away from steemit.com">80% of all messages</a> sent from one neuron to another use this neurotransmitter.</p>
<p>Glutamate is excitatory, which means it promotes action. Even though 
it is an amino acid, we can't get it from our diets because of the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292164/" rel="noopener" title="This link will take you away from steemit.com">blood brain barrier.</a>
 So we have to manufacture it, in our brains.  This happens in an 
exquisitely balanced process called the Glutamate-GABA-Glutamine Cycle. 
 An important part of that cycle is the astrocyte, a cell that is 
abundantly dispersed throughout the brain.</p>
<center>[<img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmX871zxKjUKffjkoX2u46FGZEdGvmvMtm2RdJ15S7wUBS/Astrocyte5%20GerryShaw%203.0.jpg" alt="Astrocyte5 GerryShaw 3.0.jpg"><br>
<img src="https://steemitimages.com/640x0/https://commons.wikimedia.org/wiki/File:Astrocyte5.jpg"></center>
<hr>
<h5><center>Huntington's: Not Enough</center></h5>
<p>The astrocyte is like a transfer terminal.  Once glutamate has been 
used in a synapse, it is sent over to an astocyte for processing.  
Processing means converting <a href="https://nba.uth.tmc.edu/neuroscience/m/s1/chapter08.html" rel="noopener" title="This link will take you away from steemit.com">glutamate to glutamine,</a>
 and then sending the glutamine off  to a neuron, where it will be 
changed back into glutamate.  This keeps the brain humming with enough 
glutamate to carry on its work effectively.</p>
<p>However, sometimes the glutamine never leaves the astrocyte. If that 
happens, then new glutamate won't be made, and there will be a deficit 
of this vital neurotransmitter.  That's exactly what happens in <a href="https://www.sciencedaily.com/releases/2018/06/180620100605.htm" rel="noopener" title="This link will take you away from steemit.com">Huntington's</a>.  With a deficit of glutamate, there is a disruption in the transmission of nerve impulses.</p>
<hr>
<h5><center>Parkinson's:  Too Much</center></h5>
<p>As has already been established here, glutamate is an excitatory 
neurotransmitter.  There are also inhibitory neurotransmitters.  These 
depress activity.  An important <a href="https://www.psychologytoday.com/us/blog/you-illuminated/201006/your-brain-alcohol" rel="noopener" title="This link will take you away from steemit.com">inhibitory transmitter</a>
 is GABA.   Ideally, these two neurotransmitters--a positive and a 
negative, an excitatory and inhibitory--will be in balance.  In 
Parkinson's that balance is disrupted in favor of glutamate. There's <a href="https://www.hindawi.com/journals/pd/2013/196028/" rel="noopener" title="This link will take you away from steemit.com">too much excitatory</a> transmission. So much excitement, that neurons are damaged, and even killed.</p>
<p>This is where GM1 ganglioside seems to be helpful.  It seems to have <a href="https://www.karger.com/Article/Fulltext/362419" rel="noopener" title="This link will take you away from steemit.com">anti-excitatory properties</a> and neutralize the effects of glutamate. This will spare nerve cells that would otherwise die.</p>
<hr>
<h5><center>Alzheimer's: A Devastating, Unregulated Release </center></h5>
<p>In Alzheimer's, there is also a toxic bombardment of <a href="https://www.frontiersin.org/articles/10.3389/fnins.2019.00043/full" rel="noopener" title="This link will take you away from steemit.com">excitatory glutamate</a>
 The result is the death of neurons and loss of function.   Some 
medicines that have been formulated to ameliorate (temporarily) the 
symptoms of  Alzheimer's symptoms try to <a href="https://www.alz.org/alzheimers-dementia/treatments/medications-for-memory" rel="noopener" title="This link will take you away from steemit.com">stem the unregulated</a> flow of glutamate.</p>
<hr>
<hr>
<hr>
<hr>
<h2><center>Causes</center></h2>
<p>Of the three diseases considered here--Alzheimer's, Huntington's and 
Parkinson's--only the cause of Huntington's can be explained with 
absolute clarity.  It is a genetic disease.  It is dominant, which 
means, if you inherit the disease from either parent, you will become 
ill.  The disease is caused by a mutant gene, huntingtin (there are 
normal huntingtin genes, also.)  The severity of the symptoms is <a href="https://rarediseases.info.nih.gov/diseases/6677/huntington-disease/cases/53692" rel="noopener" title="This link will take you away from steemit.com">influenced by the number of generations</a>
 that have passed it along.  The more generations, the more severe the 
disease is likely to be.  Although becoming symptomatic is inescapable 
for those who inherit the gene, apparently environment can play a role 
in modifying the course of the disease.</p>
<hr>
<center><a href="https://commons.wikimedia.org/wiki/File:Huntington%27s_disease_(5880985560).jpg" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmShRB3QvqAzxrCgV4gGM1QBM3WrAEQXgSPaSqx22LCShg/Huntington's_disease_(5880985560)%20National%20Institute%20of%20Standards%20and%20Technology%20public.jpg" alt="Huntington's_disease_(5880985560) National Institute of Standards and Technology public.jpg"></a></center>
<blockquote>
<p><em>The red dots show a section of the gene called CAG 
(cytosine-adenine-guanine) sequence.  The top gene is a normal 
huntingtin (HTT) gene. The bottom gene is the mutant huntingtin (mHTT). 
 Note several repeats of  CAG  in the mutant gene.  The more repeats of 
CAG in the gene, the more severe the disease will tend to be.  With each
 generation that passes Huntington's along, repeats are added.</em></p>
</blockquote>
<hr>
<p>Alzheimer's also has a genetic component, although this is not a 
direct cause and effect relationship as it is in Huntington's.  There is
 <a href="https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet" rel="noopener" title="This link will take you away from steemit.com">familial Alzheimer's.</a>  But, as with Huntington's, it seems that lifestyle can influence the age of onset and the course of the disease.</p>
<hr>
<h3><center>Formation of Plaques in Alzheimer's</center></h3>
<center><a href="https://commons.wikimedia.org/wiki/File:Alzheimers_disease-Beta-amyloid_plaque_formation.PNG" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmf1XjprXqZFoqeF1b9F6fEPJo6NNDwMsAmohGQqscsdp1/Alzheimers2%20beta%20amyloid%20plaque%20formation%20NIH%20public.jpg" alt="Alzheimers2 beta amyloid plaque formation NIH public.jpg"></a></center>
<blockquote>
<p><em>In the diagram you can see a protein,<a href="https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease" rel="noopener" title="This link will take you away from steemit.com">Beta-amyloid 42,</a> breaking off and joining together with others to make plaques--a hallmark feature of Alzheimer's Disease</em>.</p>
</blockquote>
<hr>
<p>Of the three diseases, Parkinson's has the <a href="https://www.parkinsons.org.uk/information-and-support/does-parkinsons-run-families" rel="noopener" title="This link will take you away from steemit.com">least clear genetic association,</a> although there are families where it does seem to occur more frequently.  There is also <a href="https://www.sciencedaily.com/releases/2018/01/180125105453.htm" rel="noopener" title="This link will take you away from steemit.com">Familial Parkinson's,</a>
 which is caused by a gene mutation.  In most cases, environment and 
experience are believed to play a significant role in the development of
 Parkinson's disease.</p>
<hr>
<hr>
<hr>
<p>I began writing this blog because I had questions. The questions 
began with GM1 ganglioside, but in order to understand that I need to 
learn more about neurodegeneration.  This is not one disease, or three 
diseases. Each disease, it seems teaches us about the others.  In 
reading different articles--and I was sure to reference those published 
in the last couple of years--so much information was speculative, or 
tentative.  It's obvious that our understanding the brain, the part of 
our bodies that controls everything we do and know, is in its infancy.</p>
<hr>
<hr>
<p>I can't leave this post without acknowledging a debt to the animals 
that have suffered and died so that we may understand ourselves.</p>
<hr>
<hr>
<p><a href="https://pixabay.com/photos/animal-creature-critter-domestic-1239397/" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmZmJgNzHn5nny5NLjVYWKaXSWsgkycTxNrkKiX5RdAGFF/mouse%20huntington%20conscience.jpg" alt="mouse huntington conscience.jpg"></a></p>
<hr>
<hr>
<p><a href="https://pixabay.com/photos/lamb-passover-cute-easter-4131386/" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmRGSxMZVadHyy3BoSWZ4GufTiC6tSqTZgDVaebkkMB2t5/lamb%20huntingtons%20conscience.jpg" alt="lamb huntingtons conscience.jpg"></a></p>
<hr>
<hr>
<p><a href="https://pixabay.com/photos/fruit-fly-fly-inset-wings-flying-219391/" rel="noopener" title="This link will take you away from steemit.com"><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmWixsi7NEekdKNryuvHxU5AWV1jxKX8EtzXVvNFMs9eSc/frui%20-fly%20huntington's%20conscience.jpg" alt="frui -fly huntington's conscience.jpg"></a></p>
<center><img src="https://steemitimages.com/640x0/https://cdn.steemitimages.com/DQmTDqHVniPuLrhgLZxBCzjKQYcdiCXVL6Vp6qnRSHYWKe2/accent%20accent.jpg" alt="accent accent.jpg"></center>
<hr>
<h2><center>Sources</center></h2>
<blockquote>
<p>I did a lot of background reading for this piece.  Most of the sources mentioned here were directly referenced.</p>
</blockquote>
<hr>
<hr>
<hr>
<h5>One of my sources was <a href="https://steemit.com/@chappertron">@chappertron</a>.
  He described (in one of his comments) the effect that varying levels 
of glutamate had on different animals.  That sent me reading in a very 
productive direction. Thank you, <a href="https://steemit.com/@chappertron">@chappertron</a>!</h5>
<hr>
<hr>
<hr>
<h3><center>References</center></h3>
<h6><center>Footnote</center></h6>
<hr>
<p><sup><a href="https://steemit.com/submit.html#footnote1" rel="noopener" title="This link will take you away from steemit.com">1</a></sup>  <em>Frontiers in Molecular Biosciences</em> <a href="https://www.frontiersin.org/articles/10.3389/fmolb.2019.00020/full" rel="noopener" title="This link will take you away from steemit.com">Protein Misfolding and ER Stress in Huntington's Disease</a> Talya Shacham, Neeraj Sharma, and Gerardo Z. Lederkremer</p>
<hr>
<hr>
<h6><center>Sources</center></h6>
<hr>
<p><em>The Guardian</em>: <a href="https://www.theguardian.com/science/2017/jul/08/medical-research-transgenic-sheep-huntingtons-disease" rel="noopener" title="This link will take you away from steemit.com">Scientists deploy GM sheep in fight to treat Huntington’s disease</a></p>
<p><em>Aljazeera</em>: <a href="http://america.aljazeera.com/features/2014/1/when-the-hard-travelinawasoverwoodyguthrieatgreystonehospital.html" rel="noopener" title="This link will take you away from steemit.com">The lost years of Woody Guthrie: The singer's life in Greystone Hospital</a></p>
<p><em>Oxford Academic</em>:  Glycobiology  <a href="https://academic.oup.com/glycob/article/17/1/1R/715963" rel="noopener" title="This link will take you away from steemit.com">Gangliosides as components of lipid membrane domains</a></p>
<p><em>Frontiers in Molecular Neuroscience</em> <a href="https://www.frontiersin.org/articles/10.3389/fnmol.2019.00020/full" rel="noopener" title="This link will take you away from steemit.com">Role of Metabotropic Glutamate Receptors in Neurological Disorders</a></p>
<p><em>Advances in Experimental Medicine and Biology</em> <a href="https://link.springer.com/chapter/10.1007/978-1-4684-1200-0_28" rel="noopener" title="This link will take you away from steemit.com">Ganglioside Receptors: A Brief Overview and Introductory Remarks</a></p>
<p><em>Cells</em> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972652/" rel="noopener" title="This link will take you away from steemit.com">How Do Gangliosides Regulate RTKs Signaling?</a></p>
<p><em>GARD</em>  <a href="https://rarediseases.info.nih.gov/diseases/10891/gm1-gangliosidosis" rel="noopener" title="This link will take you away from steemit.com">GM1 gangliosidosis </a></p>
<p><em>Progress in Molecular Biology and Translational Science</em> <a href="https://www.ncbi.nlm.nih.gov/pubmed/29747823" rel="noopener" title="This link will take you away from steemit.com">Gangliosides, α-Synuclein, and Parkinson's Disease</a></p>
<p><em>Huntington's Disease in High Definition</em> <a href="https://www.hdinhd.org/feed-items/disease-modifying-effects-of-ganglioside-gm1-in-huntingtons-disease-models/" rel="noopener" title="This link will take you away from steemit.com">Disease-modifying effects of ganglioside GM1 in Huntington's disease models</a></p>
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<p><em>Journal or Neurological Science</em> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532888/" rel="noopener" title="This link will take you away from steemit.com">A Randomized, Controlled, Delayed Start Trial of GM1 Ganglioside in Treated Parkinson’s Disease Patients</a></p>
<p>Glyco Science Research, Inc.  <a href="http://www.glycoscienceresearch.com/exec-summary/" rel="noopener" title="This link will take you away from steemit.com">Executive Summary of Ovine GM1 Ganglioside Project</a></p>
<p><em>Arq Bras Oftalmol</em> <a href="https://www.ncbi.nlm.nih.gov/pubmed/19820796" rel="noopener" title="This link will take you away from steemit.com">'Cherry red spot' in a patient with Tay-Sachs disease: case report</a></p>
<p><em>Scientific Reports</em> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974419/" rel="noopener" title="This link will take you away from steemit.com">Induction of ganglioside synthesis in Drosophila brain accelerates assembly of amyloid β protein</a></p>
<p><em>Neuroscience News and Research</em> <a href="https://www.technologynetworks.com/neuroscience/articles/unlocking-the-secrets-of-brain-organization-in-the-fruit-fly-310488" rel="noopener" title="This link will take you away from steemit.com">Unlocking the Secrets of Brain Organization -in the Fruit Fly</a></p>
<p><em>ACS Omega</em>  <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793032/" rel="noopener" title="This link will take you away from steemit.com">Sphingomyelin and GM1 Influence Huntingtin Binding to, Disruption of, and Aggregation on Lipid Membranes</a></p>
<p><em>YouTube</em>  <a href="https://www.youtube.comQBWlIW32N8E" rel="noopener" title="This link will take you away from steemit.com">Michigan Breeders Aim to Cure Huntington's</a></p>
<p><em>Cold Spring Harbor Perspectives on Biology</em> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140680/" rel="noopener" title="This link will take you away from steemit.com">Voltage-Gated Calcium Channels</a></p>
<p><em>Critical Care Clin.</em> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381605/" rel="noopener" title="This link will take you away from steemit.com">The Role of Plasmapheresis in Critical Illness</a></p>
<p><em>Northwestern University</em> <a href="https://www.scholars.northwestern.edu/en/publications/synaptopathies-synaptic-dysfunction-in-neurological-disorders-a-r" rel="noopener" title="This link will take you away from steemit.com">Synaptopathies: synaptic dysfunction in neurological disorders – A review from students to students</a></p>
<p><em>Concussion Legacy Foundation</em> <a href="https://concussionfoundation.org/CTE-resources/what-is-CTE" rel="noopener" title="This link will take you away from steemit.com">What is CTE?</a></p>
<p><em>Loyola University</em> <a href="https://ecommons.luc.edu/luc_diss/2586/" rel="noopener" title="This link will take you away from steemit.com">Endocytic Vesicle Rupture in the Pathogenesis and Propagation of Neurodegenerative Proteinopathies</a></p>
<p><em>Neurology</em> <a href="https://n.neurology.org/content/91/23_Supplement_1/S26.3" rel="noopener" title="This link will take you away from steemit.com">Propagating prion-like amyloid proteins invade target cells through endocytic vesicle rupture</a></p>
<p><em>Cold Spring Harbor Perspectives in Medicine</em>  <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281589/" rel="noopener" title="This link will take you away from steemit.com">α-Synuclein in Parkinson's Disease</a></p>
<p><em>Molecular Cell</em>  <a href="https://www.cell.com/molecular-cell/pdf/S1097-2765(18)30277-6.pdf" rel="noopener" title="This link will take you away from steemit.com">ArticleA Liquid to Solid Phase Transition UnderlyingPathological Huntingtin Exon1 Aggregation</a></p>
<p><em>Medical Press</em>  <a href="https://medicalxpress.com/news/2018-07-big-alzheimer-scientists-id-genesis.html" rel="noopener" title="This link will take you away from steemit.com">The 'Big Bang' of Alzheimer's: Scientists ID genesis of disease, focus efforts on shape-shifting tau</a></p>
<p><em>PLOS One</em>  <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873140/" rel="noopener" title="This link will take you away from steemit.com">Comparison
 of mHTT Antibodies in Huntington’s Disease Mouse Models Reveal Specific
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Development</a></p>
<p><em>BrightFocus Foundation</em> <a href="https://www.brightfocus.org/alzheimers-disease/infographic/amyloid-plaques-and-neurofibrillary-tangles" rel="noopener" title="This link will take you away from steemit.com">Amyloid Plaques and Neurofibrillary Tangles</a></p>
<p><em>Science Daily</em> <a href="https://www.sciencedaily.com/releases/2016/02/160203134848.htm" rel="noopener" title="This link will take you away from steemit.com">Structure of brain plaques in Huntington's disease described</a></p>
<p><em>Movement Disorder</em>  <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478091/" rel="noopener" title="This link will take you away from steemit.com">Amyloid deposition in Parkinson Disease and Cognitive Impairment: A Systematic Review</a></p>
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<p><em>The Brain From Top to Bottom</em>  <a href="https://thebrain.mcgill.ca/flash/i/i_01/i_01_m/i_01_m_ana/i_01_m_ana.html" rel="noopener" title="This link will take you away from steemit.com">Synapses</a></p>
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<p><em>Science Daily</em>  <a href="https://www.sciencedaily.com/releases/2018/06/180620100605.htm" rel="noopener" title="This link will take you away from steemit.com">New piece in the Huntington's disease puzzle</a></p>
<p><em>Psychology Today</em> <a href="https://www.psychologytoday.com/us/blog/you-illuminated/201006/your-brain-alcohol" rel="noopener" title="This link will take you away from steemit.com">Your Brain on Alcohol</a></p>
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<p><em>Alzheimer's Association</em>  <a href="https://www.alz.org/alzheimers-dementia/treatments/medications-for-memory" rel="noopener" title="This link will take you away from steemit.com">Medications for Memory</a></p>
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<p><em>Nature</em>  <a href="https://www.nature.com/articles/d41586-018-05177-y" rel="noopener" title="This link will take you away from steemit.com">CRISPR
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<p><em>National Institute on Aging: Causes of Alzheimer's Disease</em>   <a href="https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet" rel="noopener" title="This link will take you away from steemit.com">Alzheimer's Disease Genetics Fact Sheet</a></p>
<p><em>National Institute of Aging</em>  <a href="https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease" rel="noopener" title="This link will take you away from steemit.com">What Happens in the Brain with Alzheimer's</a></p>
<p><em>Science Daily</em>  <a href="https://www.sciencedaily.com/releases/2018/01/180125105453.htm" rel="noopener" title="This link will take you away from steemit.com">Mechanism of familial Parkinson's disease clarified in fruit fly model</a></p>