Disease Motifs
Investigating the Biomechanics of Disease
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Parkinson's Disease (PD)

The script picked up 95 proteins with some association with Parkinson's disease, two of which were discarded for being false positives so leaving 93 proteins that are looked here. This work has been done with a database that was downloaded from the EBI on the 7th & 8th of January 2017.

To see the protein sequence analysis on the proteins that are associated with Parkinson's disease click on this link Protein sequence analysis of Parkinson's disease

Journal of Alzheimers Disease & Parkinsonism

Preliminary set theory-type analysis of proteins associated with Parkinson's disease
- published paper 2014


In an attempt to create a model of Parkinson's disease (PD) eighty-three proteins were extracted from the Swiss-Prot protein database that had some casual mention of PD. These were split up into various subsets of proteins of which three are focused on here: PARK, made up of proteins that had some indication that polymorphisms in the protein might increase a person's susceptibility to develop PD; MITOCHOND, proteins which had some association with the mitochondria; and MT-C1D, proteins that were implicated in mitochondrial complex 1 deficiency. The PARK subset had 21 out of 83 proteins (21/83); MITOCHOND 33 out of 83 proteins (33/83); and MT-C1D 17 out of 83 proteins (17/83). The results could be used to build up a basic model of PD creating phenotypes based on sets of proteins. The main phenotypes established here are; non-mitochondrial PD (50/83) and mitochondrial PD (33/83). Further division is possible dependant on whether proteins have polymorphisms which increase susceptibility to develop PD. MT-C1D seems to be independent of the PARK set. This is a very simplistic attempt at trying to model Parkinson's disease at the proteomic level and will need further work to build up the more complex and realistic PD proteomic disease model.

Theoretical Biological Switch which may Play an Important Role in Parkinson's Disease, Schizophrenia, Hyposmia and the Onco-Parkinson's Mechanism


Antagonists against the Histamine Receptor H2 (HRH2_HUMAN) protein may have some efficacy in reducing levodopa-induced dyskinesia in Parkinson's Disease

Using short sequence proteomic analysis on the histamine receptor 2 which involves splitting this protein sequence into smaller fragments of ten amino acids and contrasting (using BLAST) against the human protein database.

Three main motifs were found; with the initial two being named the CW-motif and the NxxxNP-motif, with the adjacent amino acid residues being important. The third motif NPxxY overlays the end of the NxxxNP-motif and may form part of a rhodopsin NPxxY(x)5,6F type motif but in this case, it is a variant form NPxxY(x)6,7F present in many of the serotonin and dopamine receptors found here. Using the variants of NPxxY found in the dopamine and serotonin receptors, as a specific amino acid search-term (non-BLAST), it was found that a high proportion of the proteins returned were olfactory proteins.

This small region of similarity amongst dopamine, serotonin and olfactory receptors might be suggestive of a biological switch which might play an important role in Parkinson's disease, schizophrenia and the onco-Parkinson's effect seen in people with Parkinson's disease (who may have raised or lower risk of developing certain types of cancer).

Cancer associated with Parkinson's Disease (Oncological Parkinson's Disease)

Consisting of 41 proteins that have some mention of PD and 'possibly' cancer. Some of these have no polyphorphisms connected with the increased chance of developing a particular disease.

We have some smaller subsets mostly contained within this larger cancer set

Alzheimic Parkinson's Disease

Consisting of 11 proteins that have some mention of Alzheimer's Disease and PD. One of these has no polyphorphisms connected with the increased chance of developing a particular disease.

Alzheimer's disease

There are a total of 96 proteins that seem to have some mention of Alzheimer's disease within the comments section of the protein datasheet. None were excluded. This work was done using a database that was downloaded from the EBI on the 7th & 8th of January 2017.

To see the protein sequence analysis on the proteins that are associated with Alzheimer's disease click on this link Protein sequence analysis of Alzheimer's disease

Proteomic Analysis of the Amyloid Precursor A4 Protein Proteomic Analysis of the Amyloid Precursor A4 Protein

Not published in scientific journal but this paper is available as an e-paper for £3.99 exVAT. This is just a five page article or paper but will help fund my work.


This work demonstrates the principle of using sequence similarity to link possible causative microbial pathogens to particular parts of proteins that are associated with a particular disease. A small 10 amino acid sequence of amyloid precursor protein, including residues 711 and 713, were matched against the viral Swiss-Prot protein database for sequences of close similarity. This was conducted in the amino-carboxyl direction (NC) but also in the reversed direction (CN) i.e. the sequence was reversed. In the reversed (CN) direction two small three amino-acid (Valine-Isoleucine-Alanine and Valine-Glycine-Glycine) motifs were found in the capsid protein from the Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV). This possibly suggests that there might be some link between these viral proteins and the amyloid precursor protein which may be more apparent in people who become infected with either of these two viruses e.g. People who die from infection of the virus may have an increased level of beta amyloid 40 or 42.

Prion Diseases (CJD FFI and GSS)

Three dimensional structure of HuPrP(90-231 M129 Q212P).  DOI:10.2210/pdb2kun/pdb  2KUN.  Image produced courtesy of RCSB PDB
Human Prion Protein showing amino acid residue 90 to 231 containing the Q212P mutation that is believed to increase the probablity of an individual developing Gerstmann-Sträussler-Scheinker Disease GSS.
Image courtesy of the RCSB PDB
Some basic research into Prion diseases such as CJD, GSS and FFI. Largely work done on the prion protein as well as Cystatin-C and Gamma-enolase. The latter two more in regarding CJD.

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