Introduction to Parkinson's Science/Site Map

This is a Draft Outline of Part 2: The Science behind Parkinson’s with links to subpages already created and to stubs of pages to be developed.

Draft Page structure

The main subpages: narrative Q&A pages providing pathways through the entire material of Section 2.

Background Information boxes: also subpages of Section 2 which expand upon a topic that is important for understanding the science of Parkinson's. Pointed to by the narrative subpages. PD Specific. They may simply be the details of a topic that is mentioned or summarised in one of the main narrative (Q&A) pages.

Other related background topics boxes : basic biology or other information. Links to pages already written in Section 1 and to existing material out there on the web (e.g. in Wikipedia). But if such a link is not quite appropriate we shall have to write our own pages.

The Section 2 Site Map below is based on this draft page structure. There are links to existing subpages. Stub subpages can be set up and links can be put to them on this Site map. Then we can invite individuals to select a page and go straight in and add the material and links.

See footnotes for numbering and naming of subpages.

Site Map - Subpages created and started

Presenting symptoms, diagnosis and prognosis

Question Page 1. URL: Introduction_to_Parkinson's_Science/Q_Page_1

Questions addressed:

• What has caused me to have Parkinson's?
• Does Parkinson's affect life expectancy?
• Is it contagious?
• What are the usual early symptoms and what confirms the diagnosis?
• How does the disease progress?

Motor symptoms and dopamine

Question Page 2. URL: Introduction_to_Parkinson's_Science/Q_Page_2

Questions addressed:

• What causes the motor symptoms?
• What is dopamine and what does it do?
• Why is there a lack of dopamine?
• Why and how does lack of dopamine affects movement?

Content outline is on the talk page of the subpage: Talk:Introduction_to_Parkinson's_Science/Q_Page_2

More on effect of lack of dopamine

Question Page 3. URL: Introduction_to_Parkinson's_Science/Q_Page_3

Questions addressed:

• How exactly are the basal ganglia circuits affected by the lack of dopamine?

Content outline is on the talk page of the subpage: Talk:Introduction_to_Parkinson's_Science/Q_Page_3

Other PD symptoms

Question Page 40. URL: Introduction_to_Parkinson's_Science/Q_Page_40

Questions addressed:

• What other symptoms, especially non-motor symptoms, of Parkinson’s are there?

Bladder and bowel, olfaction, speech and swallowing, depression, dementia. The life cycle of Parkinson’s.

• What are the origins of these symptom?

Other brain areas that are affected by the disease. The Braak staging hypothesis and the evidence for it beginning in the Enteric Nervous System and in the myocardial nerves.

Current therapies for PD

Question Page 50. URL Introduction_to_Parkinson's_Science/Q_Page_50

Questions addressed?

• What are the drugs that I take meant to do and what symptoms do they address?

• What treatments are there for the other symptoms?

Content outline is on the talk page of the subpage: Talk:Introduction_to_Parkinson's_Science/Q_Page_50

How Parkinson's spreads through the nervous system

Question Page 90 - Introduction_to_Parkinson's_Science/Q_Page_90

(This leads to a discourse on the pathological signs – Lewy pathology, alpha-synuclein deposition. This will require an explanation of basic biochemistry.) For Background information (general):

Proteins:

Expression, structure (shape and folding), function

(Braak staging theory) Probably needs a supplementary page for a fuller explanation in Background information (PD Specific)

Is Parkinson's Disease inherited?

Question Page 120 - Introduction_to_Parkinson's_Science/Q_Page_120

(Summary of gene variations linked with Parkinson's and GWAS) For Background information (PD Specific)

Pages for the PARK genes and how they are thought to give rise to pathogenesis)

Gene association and combinations

For Background information (general)

Relevant genetics topics

What are mutations?

Base pairs, genotypes, SNPs and gene notation

To add a topic or question Please Login first. (Create an account if you have not got one yet.) See if your topic or question is already here. If so, you can go to the page and add or expand an answer If not, add your topic or question: If you are ready to do so, go to an appropriate place in this Site Map. Use similar text to another entry and create a new empty subpage Type {{subst:PD_Sci_Intro_Page}} into the empty subpage and save it. This will copy in a template to produce the standard layout with all the standard boxes. Then write an answer or just start one for others to help complete. Any part of this wikiversity project can be worked on by anyone. If there is something that is missing or needs further elaboration, then just add it! (Please back up all the assertions you make with references to external sources.) Discuss changes Use the Discussion tab at the top of the page if you want to discuss possible changes in advance, make suggestions, ask a question that others may be able to answer or ask other people's opinions.

Site Map - Subpages proposed

Causes of nerve cell death

Question Page 60. URL: Introduction_to_Parkinson's_Science/Q_Page_60

Questions addressed:

• What causes the cells to misfunction and die in PD?
• What makes dopamine-producing neurons in the substantia nigra so vulnerable?

(This should simply summarise the major topic on causes of dopamine cell death and what strategies can be proposed to prevent it. It would also lead to a discussion of cell-replacement strategies.)

(It should also explain why it is thought that dopaminergic cells are so vulnerable while others cells are not. It should mention that neurons in other parts of the nervous system are affected but generally not so extensively or with so much degeneration.)

(So there will be some branching at this point. Page 60 will mention the various factors involved in cell death – oxidative stress, mitochondrial dysfunction, genetic factors etc but (a) all these terms will have to be explained in Background information PD-specific or general pages and (b) there will need to be normal narrative pages for each topic as the Science of Parkinson's is elaborated.

What could slow down or prevent nerve cell death?

Question Page 70 - Introduction_to_Parkinson's_Science/Q_Page_70

(Neuroprotective strategies.)

Links to questions later on

For Background information (PD-specific) – Linkto Section 1 PD_Neuroprotection pages

Could the lost cells be replaced?

Question Page 80 - Introduction_to_Parkinson's_Science/Q_Page_80

(Cell-replacement strategies – foetal transplants, Neural Stem Cells, iPSCs)

For Background information (PD-specific) – Link to Section 1 stem cell pages

How and why is abnormal alpha-synuclein damaging to cells?

Question Page 100 - Introduction_to_Parkinson's_Science/Q_Page_100

(Alpha-synuclein is present in many cells and its function is not fully known but it appears to be involved in certain specified ways. The problem arises when molecules start to join together firstly as small oligomers and then as higher order aggregates. It appears that some of the small oligomers are toxic rather than the aggregates. The aggregated forms could be an attempt by the body to remove the toxic forms. The question is why the normal garbage collection systems are not able to remove the toxic forms. Viscious circle, self reinforcinging process) For Background information (PD specific and/or general)

An explanation of autophagy, the UPS and the innate and adaptive immune systems. In some cases it might be a fault in one of these systems that allows Parkinson’s to develop.

What other pathological processes are present in Parkinson's?

Question Page 110 - Introduction_to_Parkinson's_Science/Q_Page_110

(Inflammation, mitochondrial dysfunction, oxidative stress, apoptosis/programmed cell death.) Background information (PD Specific)

More detailed separate pages on inflammation, mitochondrial dysfunction, oxidative stress, apoptosis/programmed cell death etc with links to Section 1 and wikipedia.

What are the main lines of PD research?

Question Page 130 - Introduction_to_Parkinson's_Science/Q_Page_130

Summary page.

Then each topic needs a separate page:

Understanding the disease.

Toxicology, pharmacology, biochemistry, proteomics, metabolomics, pathology, aetiology

Better Model systems – in vitro, in vivo, animal models, use of iPSCs.

Genetic modification

Drug screening

Epidemiology

Search for biomarkers for early diagnosis and biomeasures for rate and stage of disease progression.

Finding other potential treatments and therapies:

Neuroprotective strategies and why.

Inflammation, ant-inflammatories and immunology

Antioxidants and why.

Vaccination against and disaggregation of alpha-synuclein

Growth factors. GDNF etc.

Transplantation

Gene therapy

Exercise – symptomatic treatment or disease modification?Research methods

Other causes that may suggest other effective therapies:

Genetics

Mitochondrial dysfunction.

What are the latest hypotheses about Parkinson's pathogenesis

Question Page 140 - Introduction_to_Parkinson's_Science/Q_Page_140

Overview of aetiology and pathogenesis – towards a unified theory.

Include hypotheses for the way it spreads (incl prion-like process)

Background information pages to be linked to where appropriate:

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For Other background information topics:

More basic cell biology

DNA

How cells express themselves

(A discussion of proteins – that there are so many different ones which do all the essential things in the body. That they are expressed by the genes. That differences in their chemical composition lead them to having different shapes and that a combination of their chemical composition (functional groups) and their shape determine how they will interact with other proteins and therefore how they will function)

How cells differentiate themselves

(Differentiation and introduce the topic of stem cells)

How cells reproduce themselves

(Distinguish between prokaryotic and eukaryotic reproduction and this might be a good point to introduce the workings of viruses and prions)

Footnotes