Research Proposal

Amyotrophic Lateral Sclerosis (ALS) loss of neurons in the motor cortex, brainstem, and
spinal cord” (The ALS Association, 2019) causes a lot of deaths in people and there is not any
certain treatment for it. Many patients will die early by the age of 50 to 65 due to this disease.
ALS affects the frontal and temporal lobes of the brain associated with speaking, personality, and
behavior. A person who has ALS will be paralyzed and finally will die. The 10% percent of ALS
associated diseases are due to genetic mutations and 90% are caused randomly. According to the
ALS Association “Every day, an average of 15 people are newly diagnosed with ALS- more than
5,600 people per year. As many as 30,000 Americans may currently be affected by ALS and
annually, ALS is responsible for two deaths per 100,000 people.” As Tiryaki and Horak explain
in “ALS and other motor neuron diseases”.
As of 2014, two-thirds of familial ALS and 10% of sporadic ALS can be explained by
genetics. TAR DNA binding protein 43 kDa (TDP-43), for instance, has been shown to cause
frontotemporal dementia as well as some cases of familial ALS and is associated with
frontotemporal dysfunction in ALS. (Ovid, Ezgi Tiryaki; Holli Horak, October 2014). In ALS
TDP-43 genes are highly phosphorylated (getting a Phosphate group from kinases) and they start
to misfold and aggregate in a brain. When proteins aggregate, they lose their function and
activity. Neurons are made of soma, a dendrite, and an axon. Since dendrites are made of
proteins, they send messages to other neurons and cause electrical pulses, but when they
aggregate, they cannot send any messages out and that causes the disruption in the body activity
such as losing the ability to talk and walk.
Recently, it has found that changes in the endoplasmic reticulum (ER) may lead to
the collection of misfolded proteins. This possibly due to either hereditary absconds or post-
translational modifications in the ER. To preserve cell reasonability, ER stretch initiates a
versatile response, the unfolded protein reaction (UPR). “The UPR triggers a network of
signaling cascades, which inhibit protein translation while up-regulating protein folding
chaperones and cell-clearing systems”( Endoplasmic Reticulum Stress in Disease Pathogenesis).
Those reactions happen in the specific stress sensors and activate those that control the protein
folding. When sever stress happens in the ER, the UPR changes into the UPR cell-mediated
death and causes a lot of disorderedly in the central nervous system.
In this research project, I am interested in seeing if early treatments such as learning,
practicing, and reading can prevent this disease from progression. Learning is basically the
method of recording data absent and recovering it again. Learning happens when the brain
reinforces or makes modern neural associations or makes these associations more viably. Neural
connections (crevices between neurons) and neurons are central to this handle. Neurotransmitters
are chemicals that make distinctive chemical responses in our brain, permitting us to do, think, or
keep in mind anything. Common cases of these chemicals are “serotonin, norepinephrine and
acetylcholine” (Chemistry of Learning), but there are 35 or more neurotransmitters everybody
utilizes every day. These chemicals are made from amino acids from dietary protein, whereas
various vitamins and minerals required for their generation. Particularly “vitamin B-6, folic
corrosive, niacin, press and vitamin C” (Chemistry of Learning) are central to sound brain work.
Receptor molecular on the closes of neurons pass on, halt, or control the chemicals depending on
the sort of neurotransmitter. Ionotropic receptors can be energized by neurotransmitters like
glutamate and aspartate and repressed by neurotransmitters like GABA and glycine. Most
neurotransmitters receptors are G-protein coupled receptors or Metabotropic receptors which are
not one or the other excitatory nor inhibitory, but instep balance the activities of excitatory and
inhibitory neurotransmitters, therefore in this research paper I would like to see if learning and
practicing constantly during ALS causes the patients to live longer since learning has the direct
effect with neurotransmitters such as GABA and we know that increase in GABA is due to
decrease in Glutamate which causes ALS?
The methods that I want to use in this research is to have two different groups of patients
that are diagnosed with ALS and they have this disease for three to four years and for one group
I want them to study, practice, and learn new activities continuously and for the other group is
not given any new practices and after a period of time we will look at the EMG from those
patients and will see if the neural plasticity has been increased? The timeframe that is expected
for this research is six months and more. The expected result is learning constantly causes
slowing down the neurodegenerative processes and will help ALS people to live longer.

References

“Quick Facts About ALS & The ALS Association.” ALSA.org, 2005,
http://www.alsa.org/news/media/quick-facts.html
“Tardbp TAR DNA Binding Protein [Mus Musculus (House Mouse)] - Gene - NCBI.” National
Center for Biotechnology Information, U.S. National Library of Medicine,
https://www.ncbi.nlm.nih.gov/gene/230908.
“The Chemistry of Learning.” Www.ChemistryIsLife.com, http://www.chemistryislife.com/the-
chemistry-of-learning.
Lin, Jonathan H, et al. “Endoplasmic Reticulum Stress in Disease Pathogenesis.” Annual Review
of Pathology, U.S. National Library of Medicine, 2008,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653419/.
Parkin Kullmann, Jane Alana, et al. “Is Psychological Stress a Predisposing Factor for
Amyotrophic Lateral Sclerosis (ALS)? An Online International Case-Control Study of
Premorbid Life Events, Occupational Stress, Resilience and Anxiety.” PloS One, Public
Library of Science, 21 Sept. 2018,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150536/.
Tiryaki, Ezgi, and Holli Horak. “American Academy of Neurology.” October 2014 - Volume 20
Issue 5: CONTINUUM: Lifelong Learning in Neurology,
https://journals.lww.com/continuum/Abstract/2014/10000/ALS_an.
Zarei, Sara, et al. “A Comprehensive Review of Amyotrophic Lateral Sclerosis.” Surgical
Neurology International, Medknow Publications & Media Pvt Ltd, 16 Nov. 2015,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653353/.