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Self-Destructive Processes

Parkinson’s Disease is characterized by a number of ongoing processes: Neuroinflammation and Inflammation, Mitochondrial Failure, Oxidation, Microglial Activation, Altered Stress Response, Endothelial Failure,  Autoimmunity, Misfolding Proteins, Excitotoxicity,   – all play a role to one extent or another in the course of Parkinson’s Disease. There are almost certainly others. We really can’t understand PD without understanding, at least in general, these factors.

Inflammation Inflammation is a response by the body to infection, injury, irritation, stress, or diet. We usually think of it as fending off invading microorganisms, which it is, but that is a rather limited view. Infection by these tiny creatures is just one trigger of a process that includes not only the destruction of foreign creatures, but also the removal of damaged tissues and waste, the repair of injury, the formation of protective scar tissue, and other steps to put things to rights. The response is more complex than just that, however, and is a part of our reaction to stressors, certain foods, and autoimmune problems.

Neuroinflammation– A further layer of complexity is added with the involvement of the central nervous system (CNS), the brain itself. Specialized defenders, the microglia and astrocytes,  come into play. And, where inflammation is usually a finite acute phenomenon, an open-ended chronic response is common in the CNS and lies at the heart of neurodegenerative disorders such as PD. This is the milieu of the mind itself, and we are affected by the constant interaction between our internal chemistry and the external world. In PD there is a fundamental imbalance here that, in addition to contributing to the title of this blog, expresses itself on multiple levels – from neurotransmitter supplies to how we live our lives. It is here that, like the crossroads of ancient trading empires, we find the intersection of not just inner and outer, but also multiple systems as well as mind and body, all interacting and affecting the others. It is this rich complexity that has made PD such a difficult puzzle for so long.

Mitochondrial Failure These are the energy converters that power every cell in the body. Their efficiancy slips in PD and there is less energy available to power the rest of the system. Oxidation goes up and inflammatory byproducts increase. Damage accumulates and efficiancy decreases further. A downward spiral becomes the norm.

Oxidation The conversion of matter into energy is required for life to exist and this conversion inevitably produces wastes which, if allowed to accumulate, will overwhelm a closed system. At the cellular level, these wastes include molecules that act like tiny drops of acid which “burn” surrounding tissues. The body has mechanisms which neutralize these tiny dangers quite efficiently under normal conditions. However, in the PD brain these mechanisms become inefficient while, at the same time, the waste load increases. The result is the slow burn of oxidation, an end product of these other processes,

Microglial Activation – The central feature of the neuroinflammatory process is the activation of the microglia. These miniature warriors serve as sentries and defend against invaders while the rest of the immune system gathers its forces and rushes to the fray. Then the microglia can stand down. Unfortunately, in PD this fails to happen and the microglia become chronically active. This results in accidental damage to thevery tissues the microglia seek to protect.

Altered Stress Response – The endocrine system and its stress circuits serve multiple roles. One of those is the production of cortisol, a hormone that controls inflammation. Cortisol also, however, “revs up” the body to face threats. As such, it is not intended to be a chronic feature and is destructive in that role. Unfortunately, chronic inflammation means chronic cortisol. A state of imbalance becomes the norm as the body becomes trapped in a futile attempt to put things to rights.

Endothelial Failure – Our bodies erect barriers to separate various aspects of their existence from one another. Among the most important are the barriers along the gut and that which protects the brain. Both are made up of tightly interlocking cells which allow certain substances to pass while preventing others. Unfortunately, inflammation disrupts these barriers and allows toxins access to the brain itself.

Autoimmunity– Endothelial failure has another effect in that it allows molecules of proteins to pass through the wall of the gut where they encounter the immune system. This can set up an autoimmune response due to similarities with the body’s own proteins.

Misfolding Proteins – Alpha-synuclein clumps form in the brain and result in increased inflammation.

Excitotoxicity – Certain food additives contribute to neurodegeneration by overstimulating neurons to the point of death.

All these processes are ongoing in PD. Inflammation and mitochondrial problems lead to oxidative damage. Microglial responses lead to cell death and disturb neurofunction. Stress and inflammation allow toxins into the brain while also stressing the system.

One Comment leave one →
  1. Richard permalink
    May 24, 2011 6:33 pm

    Very good summary. Collectively and/or individually, these process likely account for the PD condition!

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