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 structureEdit
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 scence 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.
Site Map - Subpages created and startedEdit
Presenting symptoms, diagnosis and prognosisEdit
Question Page 1. URL: Introduction_to_Parkinson's_Science/Q_Page_1
- 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 dopamineEdit
Question Page 2. URL: Introduction_to_Parkinson's_Science/Q_Page_2
- 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 dopamineEdit
Question Page 3. URL: Introduction_to_Parkinson's_Science/Q_Page_3
- 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 symptomsEdit
Question Page 40. URL: Introduction_to_Parkinson's_Science/Q_Page_40
- 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 PDEdit
Question Page 50. URL Introduction_to_Parkinson's_Science/Q_Page_50
- 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 systemEdit
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):
- 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?Edit
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
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Site Map - Subpages proposedEdit
Causes of nerve cell deathEdit
Question Page 60. URL: Introduction_to_Parkinson's_Science/Q_Page_60
- 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?Edit
Question Page 70 - Introduction_to_Parkinson's_Science/Q_Page_70
Links to questions later on
For Background information (PD-specific) – Linkto Section 1 PD_Neuroprotection pages
Could the lost cells be replaced?Edit
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?Edit
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?Edit
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?Edit
Question Page 130 - Introduction_to_Parkinson's_Science/Q_Page_130
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
- 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.
- Gene therapy
- Exercise – symptomatic treatment or disease modification?Research methods
Other causes that may suggest other effective therapies:
- Mitochondrial dysfunction.
What are the latest hypotheses about Parkinson's pathogenesisEdit
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:
For Other background information topics:Edit
- More basic cell biology
- 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)
- The Q&A subpages of Section 2 - numbered to conform to a broad sequence from elementary to more advanced. (Initially they will be numbered 10, 20, 30 etc in order to allow new topics to be slotted in – 25, 35, 38 etc). But the sequence will not be considered absolute because there could be many valid paths through the material.
- The Background information pages will normally also be subpages of Section 2 but will be named rather than numbered. They will be specific to PD but if they are appropriate for accessing from Section 1 too they could be pages in their own right but would be prefixed with 'PD' so they are not seen as general Wikiversity pages.