Microglial activation is the response to multiple traumatic insults whether triggered by infection, trauma or hypoxia. This common stress response can become self-feeding and can become chronic. The authors postulate that the particular presentation (PD, ALS, Huntingtons, etc) depends on genetic variation of environmental variability.
I believe and have so believed for more than a decade that all these conditions can be remitted by blocking the perpetuation of microglial activation by the use of dopamine and seotonin precursor therapy (PURSOR).
It is becoming increasingly evident that neuroinflammation plays a crucial role in the development and progression of many neurodegenerative diseases. Glia and in particular microglia are central to mediating the effects of neuroinflammation. While neuroinflammation and microglia provide an attractive therapeutic target in the treatment and prevention of neurodegenerative diseases investigators face several challenges ahead (Appendix 2) which must be overcome before one can advocate in favor of large-scale anti-inflammatory trials in the clinic. Some of these include developing approaches to improve the access of drugs to CNS tissue as well as developing therapies that maintain or optimize the beneficial effects of neuroinflammation while eliminating or minimizing its detrimental effects.
Key Observations1. Neurodegenerative diseases are associated with signs of chronic neuroinflammation
2. A variety of initiating triggers (some as yet unknown) associated with the different neurodegenerative disorders converge at a common intersection point - activation of microglia.
3. While the initial neuroimmune response may be aimed at limiting the disease process, chronic neuroinflammation driven by persistent microglia activation is likely to aid in the progression of the disease and the hastening of neuronal demise.
4. How the inflammatory response affects specific neuronal and glial populations and contributes to specific neurodegenerative diseases remains a critical and unanswered question
Critical challenges involved in developing neuroprotective anti-inflammatory therapeutic strategies1. Identify internal and external factors that trigger chronic neuroinflammatory responses, with a focus on how acute immune responses become chronic.
2. Identify inflammatory mediators that compromise survival of specific neuronal populations.
3. Develop therapeutic compounds that cross the blood brain barrier (BBB)
4. Selectively target destructive inflammatory mediators without compromising beneficial survival-promoting effects and overall immune function.
5. Develop inclusion and exclusion criteria for human subjects to be enrolled in clinical trials taking into account their immune status."