FYI. This paper is difficult for me to understand but the general thought is that neuro-inflamation is the cause of PD. And there may be drug therapies available now (like opioid antagonists, LDN) used with early PET scans to stop progression. Dr. Hong from the NIH has published papers on this subject.
Ashley

http://www.nature.com/nrn/journal/v8...l/nrn2038.html
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms

Michelle L. Block1, Luigi Zecca2 and Jau-Shyong Hong1 About the authors
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Abstract

Mounting evidence indicates that microglial activation contributes to neuronal damage in neurodegenerative diseases. Recent studies show that in response to certain environmental toxins and endogenous proteins, microglia can enter an overactivated state and release reactive oxygen species (ROS) that cause neurotoxicity. Pattern recognition receptors expressed on the microglial surface seem to be one of the primary, common pathways by which diverse toxin signals are transduced into ROS production. Overactivated microglia can be detected using imaging techniques and therefore this knowledge offers an opportunity not only for early diagnosis but, importantly, for the development of targeted anti-inflammatory therapies that might slow or halt the progression of neurodegenerative disease.

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For many years, neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease have been a major focus of neuroscience research, with much effort being devoted to understanding the cellular changes that underlie their pathology. Microglia, the resident innate immune cells in the brain, have been implicated as active contributors to neuron damage in neurodegenerative diseases, in which the overactivation and dysregulation of microglia might result in disastrous and progressive neurotoxic consequences. Although these concepts have been widely reviewed in recent years1, 2, 3, the characteristics defining deleterious microglial activation and the mechanisms by which neurotoxic microglial activation is initiated remain poorly understood. In the current review, we therefore focus on recent reports indicating that pattern recognition receptors (PRRs) are tools used by microglia to identify neurotoxic stimuli and that stimulation of NADPH oxidase activity is the predominant mechanism through which microglia produce neurotoxic reactive oxygen species (ROS). We further explain how the identification of these crucial participants in microglia-mediated neuronal injury could provide the insight necessary for the development of novel markers that specifically define deleterious microglial activation. Furthermore, these mechanisms might be ideal prospects for targeted anti-inflammatory therapy capable of slowing and perhaps preventing neurodegenerative diseases.

In summary, inflammation-mediated neurotoxicity in neurodegenerative disease can occur as a consequence of microglial dysregulation and overactivation. Microglia monitor the brain environment by interpreting and processing stimuli (environmental toxins, endogenous proteins or reactive microgliosis) through PRRs. Several of these factors might be correctly recognized by microglia as pathogenic. However, misinterpretation of innocuous stimuli through PRRs could be a predominant mechanism through which microglia become overactivated and uncontrolled, and therefore able to exert neurotoxic effects. Although different combinations of receptors might be involved in the recognition of toxic and pro-inflammatory stimuli, there is a common deleterious downstream pathway, involving oxidative stress that both induces neuronal death and amplifies ongoing microglial activation to drive perpetuating neurotoxicity. Given the progressive and cumulative contribution of microglial activation throughout the course of neurodegenerative diseases, imaging microglia might be useful for the early identification of neurodegenerative disease. Monitoring of microglial activation throughout the disease would give an indication of when to begin anti-inflammatory treatment capable of altering disease progression, and provide feedback that allows an individually tailored therapeutic regimen based on response to therapy. Future research will need to focus on detailing the mechanisms responsible for microglial overactivation in an effort to identify more specific markers for in vivo imaging and provide the basis for the development of compounds that have greater therapeutic efficacy.