Preliminary Conclusions

About this Work

The Hypotheses

Preliminary Conclusions

Discussion

What's New: Damn near everything.

All knowledge is an expanding phenomenon and this is no exception. There are errors here and that is stipulated. It is hoped that with our combined efforts that they will be identified and corrected so that something of value will emerge.

Some Preliminary Conclusions:

PD is not simply a neurological disease, but is, instead, a combined disorder of the endocrine and immune systems further influenced by the gastrointestinal tract and manifesting with damage to the nervous system. The latter is symptom, not cause.
PD has no single cause but is the result of accumulated factors - the multiple hits hypothesis.
There is no one moment in time that marks the beginning of PD just as there is no point where a river becomes sea. Instead, there is a time of potential that can be triggered by stressful "secondary" factors.
PD arises from prenatal conditions affecting the immune and endocrine systems. This results in an ongoing struggle for homeostasis which stresses the system more with each passing year. This sets the stage for PD by creating the "potential" noted above.
Prenatal "programming" by bacterial toxins and by maternal stress hormones, both singly and jointly, alters the embryonic immune, endocrine, and nervous systems.
The resultant inflammation and imbalance of the endocrine stress systems are the core processes generating the "potential" and leading to PD.
Cytokines from inflammation and endogenous steroids from stress are neuroactive and disrupt neural function. This produces a large part of the day to day symptomology.
Microglial activation is one force driving degeneration. Mitochondrial dysfunction is a second. These drive the disorder into the advanced stages.
Effective treatment must, therefore, address inflammation, stress, mitochondrial function, microglial activation, and neurotransmitter disruption.
The cure must go further and enable neurogenesis.
While the above describes the central features of PD, the system is under continuous stress as it strives for balance/homeostasis. It is vulnerable to a number of other factors that move the potential of PD into the reality and determine the speed of its progression.
Many of these "secondary factors" synergistically react with bacterial toxins to increase the damage done and to explain some of the mysteries of PD.
Other "secondary factors" arise from the disrupted "fight or flight" center of the endocrine system - the hypothalamus, pituitary, and adrenal axis (HPAA).
The various systems involved communicate with one another from center to periphery as well as across systems in a tangle of overlapping feedback loops in which reactions change from moment to moment. This shifting complexity responding to its own constant feedback is characteristic of a non-linear or chaotic system. The logic of Newton is replaced by the madness of the Red Queen.
This complexity, although daunting, is actually a cause for hope. Chaotic systems are highly sensitive to small changes. Change one of the factors slightly and the future condition of the system changes in an amplified fashion. It should be possible to exploit this to prevent and, perhaps, even reverse a portion of the damage.

Parkinson's Disease is, within broad limits, a very individ-
ualized disorder. Each case manifests in its own way and at its own pace.

There is such a degree of variance that the assumption of a single cause has been called into question by the "multiple hits" hypothesis.

We feel even this to be too limited and propose a "menu" hypothesis where one or more core factors (the "entree") combine with secondary factors (the "side dishes") resulting in PD.

To explore this latter approach, we propose a "modular" system with each factor considered both as an independent unit and as part of a whole.

Thus, a "rotenone module" combined with a "prenatal endotoxin module" has been shown to result in neuro-
degeneration.

But to assume this to be the end of the matter would be a mistake as there are another dozen or more modules to be considered.

It is hoped that this model will bring to light a new understanding of PD.

All knowledge is an expanding phenomenon and this is no exception. There are errors here and that is stipulated. It is hoped that with our combined efforts that they will be identified and corrected so that something of value will emerge.

Some Preliminary Conclusions:

PD is not simply a neurological disease, but is, instead, a combined disorder of the endocrine and immune systems further influenced by the gastrointestinal tract and manifesting with damage to the nervous system. The latter is symptom, not cause.

PD has no single cause but is the result of accumulated factors - the multiple hits hypothesis.

There is no one moment in time that marks the beginning of PD just as there is no point where a river becomes sea. Instead, there is a time of potential that can be triggered by stressful "secondary" factors.

PD arises from prenatal conditions affecting the immune and endocrine systems. This results in an ongoing struggle for homeostasis which stresses the system more with each passing year. This sets the stage for PD by creating the "potential" noted above.

The resultant inflammation and imbalance of the endocrine stress systems are the core processes generating the "potential" and leading to PD.

Cytokines from inflammation and endogenous steroids from stress are neuroactive and disrupt neural function. This produces a large part of the day to day symptomology.

Microglial activation is one force driving degeneration. Mitochondrial dysfunction is a second. These drive the disorder into the advanced stages.

Effective treatment must, therefore, address inflammation, stress, mitochondrial function, microglial activation, and neurotransmitter disruption.

The cure must go further and enable neurogenesis.

While the above describes the central features of PD, the system is under continuous stress as it strives for balance/homeostasis. It is vulnerable to a number of other factors that move the potential of PD into the reality and determine the speed of its progression.

Many of these "secondary factors" synergistically react with bacterial toxins to increase the damage done and to explain some of the mysteries of PD.

Other "secondary factors" arise from the disrupted "fight or flight" center of the endocrine system - the hypothalamus, pituitary, and adrenal axis (HPAA).