Parkinsons Disease
gov
Symptoms: hand tremors, slow
movement, stiffness, and loss of
balance
Protein affiliated: a-synuclein is the
primary component of Lewy bodies
(abnormal aggregates of protein that
develop inside nerve cells in
Parkinson's disease)
Women over 50 affected
Treatments balance out dopamine
levels, but there are no cures
Interesting facts: Approximately 10
million people worldwide suffer from
Parkinsons disease. Around 127,000
people in the UK have the condition.
1 in every 500 people have it. It has
costed the U.S. $25 billion so far. For
medication, per patient, it costs
$2,500.
a-synuclein synthesize process:
https://www.ncbi.nlm.nih.gov/pmc/art
icles/PMC3631137/
Special thanks to Medicinenet.com, nature.com,biomedical.closeupengineering.it www.ninds.nih.
Central nervous system controlling movement is in disorder
DNA: TAC-ATA-AAC-CAA-AGA-CGG-AGG
RNA: AUG-UAU-UUG-GUU-UCU-GCC-UCC
POL.PEP.: start-tyro-lev-val-ser-ala-ser A single molecule study in 2008 suggests alpha-synuclein exists as a
1.Transcription
mix of unstructured, alpha-helix, and beta-sheet-rich conformers in
a. The partial unwinding of the DNA molecule so that the portion of equilibrium. Mutations or buffer conditions known to improve
DNA that codes for the needed protein can be transcribed.
b.Then once the DNA molecule is unwound at the correct location, an aggregation strongly increase the population of the beta conformer,
enzyme called RNA polymerase helps line up nucleotides to create a
complementary strand of mRNA
thus suggesting this could be a conformation related to pathogenic
c.The new strand of RNA is made according to the rules of the base aggregation. One theory is that the majority of alpha-synuclein
pairing
i.DNA cytosine pairs with RNA guanine aggregates are located in the presynapse as smaller deposits which
ii.DNA guanine pairs with RNA cytosine
i.DNA thymine pairs with RNA adenine
causes synaptic dysfunction. Among the strategies for treating
i. DNA adenine pairs with RNA uracil synucleinopathies are compounds that inhibit aggregation of
1.To mRNA
a.The new RNA strand is released and the two unzipped DNA strands bind together again to form the alpha-synuclein. It has been shown that the small molecule
double helix.
cuminaldehyde inhibits fibrillation of alpha-synuclein.
i.The DNA template remains unchanged after transcription, it is possible to transcribe another
identical molecule of RNA Protein synthesis relates to parkinson's because it is caused by
1.A single gene on a DNA strand can produce enough RNA to make thousands of copies of the same
protein aggregation in the brain. Given that increased protein
protein, in a very short time.
1. Then is translated
aggregation may result not only from an increase in production, but
a.mRNA is sent to the cytoplasm, where it bonds with ribosomes. There are 3 important
bonding sites; one for mRNA and two for tRNA. One is called P site and the other, A also from decreased protein clearance, it is imperative to investigate
site.
i.The ribosome slides down the mRNA, so that the tRNA in the A site moves over to both possibilities as potential PD culprits.
the P site, a new codon fills the A site. (the A site brings new amino acids to the Amino acid in the polypeptide chain is not right for that specific
growing polypeptide at the P site.
ii.The tRNA with the appropriate amino acid pairs bases with the new codon at the situation and is still used in the protein domain within the alpha helix
iii.A peptide bond forms between the two adjacent amino acids held by tRNA
molecules. This is what forms the first two links of a chain.
and/or the B sheets to misfold.
iv.The tRNA that was in the P site goes to the cytoplasm and the ribosome sliding
process begins again.
v.This continues until a stop codon enters the A site. When a stop protein enters, the
tRNA in the P site releases.
vi.Translation to the protein has completed.
1.The Protein is folded
a. The polypeptide chain is folded into alpha-helices and Beta-Sheets. (2 structure)
i.The domains are formed by combining alpha-helices and Beta-Sheet (3 structure)
1.All domains combine to form functioning protein (4 structure)