Portal talk:The Science Behind Parkinson's/Archives

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Some interesting ideas

Shall we continue the discussion started by Reverett123 and HAPE3512 here so that we can together decide where the interesting issues raised can be explored in this wiki?

Droflet (talk) 10:27, 11 October 2012 (UTC)

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I have been looking through the mound of files that are this project in search of a wiki that I developed for this same purpose a few years ago and called "Parkipedia". Thought we might be able to cannabilize it, but I have had no luck in finding it. I did, however, find a good bit in html format- http://www.parkinsonsonline.org

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0.01 - Introduction

Comment-

It is well past time for a thorough reexamination of the general view of Parkinson’s Disease. A veritable tsunami of information has been discovered in the brief time that has passed since virtually all medical practitioners and research scientists left school. Further, the nature of education is such that their instruction was almost certainly out of date at the time. The incredible volume of new findings combined with the fact that PD crosses the artificial boundaries between disciplines and the limited amount of time available to stay abreast of one’s own field makes it advisable to take a new look. The fact that PD steals lives openly and at a heartrendingly slow pace makes it essential.

Although traditionally thought of as a disease of the nervous system, PD is a disorder of multiple systems – immune, endocrine, gastrointestinal, and nervous. It is not even a disease in the usual sense of the word but is more properly a syndrome – a group of symptoms reflecting the underlying condition. Each PWP has his or her own individual portfolio of symptoms from the larger collection with some being almost universal and others being relatively rare. The causal factors are similar – a larger set from which an individual’s personal subset is drawn with some near universal and others rare. A very individualized disorder.

One word of clarification – This discussion is about Young-Onset Parkinson’s Disease. Senior-Onset may or may not be the same or a variant thereof. We leave that question to others. The reason is simple – YOPD is what we know best. The small team responsible for this work – both MD and layman – struggle with YOPD on a daily basis. This battle is personal.

In performing what is essentially a review of the literature and the work of others, we came to some conclusions that, while for the most part present in a fragmented state in the current thinking, are original and will be challenging to those into whose field we dare to trod. It is very much hoped that that will be the case and that our impudence will provoke thought and discussion.

We have come to conclude that PD is a system-wide, life-long process that must be addressed as a whole.

The process which may lead to PD begins in the womb (Pre-natal Phase), although it is influenced by events that go back generations prior to conception (Pre-conception Phase). The child is born with PD as a potential which may or may not become reality. Whether it does so or not is determined by the cumulative effects of a host of factors over the course of a lifetime.

For the most part, no one of these factors is essential to the process. But each adds in to the Potential Phase. Once the potential approaches a critical value, the systems are vulnerable to a “trigger” factor or event.

Triggers can come in many forms, but the critical point is the realization of the potential and the initiation of the next phase – the Degenerative Phase. This phase is characterized by inflammation throughout the body through the combined reactions of the immune and endocrine systems.

Inflammation increases permeability of the endothelial barriers in both the gut and the brain. Stress and inflammatory cytokines contribute to enteric nerve dysfunction and constipation. Constipation and increased endothelial permeability result in increased toxin load in the brain.

The toxin increase includes bacterial endotoxin lipopolysaccharide (LPS). Pre-natally sensitized and hypervigilant microglia respond to the LPS by release of inflammatory cytokines within the brain. Chronic exposure to cytokines results in neuronal injury and cell death. Chronic exposure to stress hormones prevents neurogenesis and repair and increases inflammation.

This is the bare framework upon which we will build a model of Parkinson’s Disease for discussion and, with luck, a new understanding from which to move forward in search of a solution.

Resources:

PD: More than a Movement Disorder, J. William Langston, M.D

"Put bluntly, it is increasingly clear that "parkinsonism" - the motor aspects of Parkinson's - is only one characteristic of what is increasingly becoming seen as a multifaceted and complex disorder."

Research:

1: Environ Health Perspect. 2005 Sep;113(9):1230-3, Early environmental origins of neurodegenerative disease in later life. Landrigan PJ, Sonawane B, Butler RN, Trasande L, Callan R, Droller D.

"Parkinson disease (PD) and Alzheimer disease (AD), the two most common neurodegenerative disorders in American adults, are of purely genetic origin in a minority of cases and appear in most instances to arise through interactions among genetic and environmental factors."

1: Glia. 2007 Apr 1;55(5):453-62. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT.

"Together, these data demonstrate that through TNFalpha, peripheral inflammation in adult animals can: (1) activate brain microglia to produce chronically elevated pro-inflammatory factors; (2) induce delayed and progressive loss of DA neurons in the SN. These findings provide valuable insight into the potential pathogenesis and self-propelling nature of Parkinson's disease."

1: Rev Neurosci. 2007;18(3-4):209-22. Stress as a modulator of motor system function and pathology. Metz GA.

"Stress can modulate movement through activation of the hypothalamic-pituitary-adrenal axis and via stress-associated emotional changes. The dopaminergic system seems to play a central role in mediating the effects of stress on motor function. This route might also account for the finding that stress influences the pathology of dopamine-related diseases of the motor system, such as Parkinson's disease. Clinical observations have indicated that stress might lead to the onset of Parkinsonian symptoms or accelerate their progression."

1: Cell Transplant. 2006;15(3):239-50. Progressive dopamine neuron loss in Parkinson's disease: the multiple hit hypothesis. Carvey PM, Punati A, Newman MB.

"Thus, the multiple hit hypothesis of PD-that is, the effect of more then one risk factor-may be the start of new era in animal models of PD that is one step closer to mimicking the pathology of PD in humans."

OK, so it won't be simple. I'll keep at it. Reverett123 (talk) 23:47, 11 October 2012 (UTC)

Hi Reverett123. I have written on your Talk page too about the changes you recently made to a subpage which unfortunately affected the front page.

Droflet (talk) 13:19, 12 October 2012 (UTC)