Jim-
I won't suggest anything since I honestly don't know at this point. However, it would seem that a sensible strategy would be to follow me down the doxycycline trail which would allow the comparison of our individual experience of a common phenomenon. We can let future generations work through individual compounds themselves. Doxycycline is one of the tetracycline family and is very similar to minocycline, another family member frequently mentioned in this context. While side effects are rare, the possible ones for the latter are more intimidating than those for the former. Both cross the BBB and are fat-soluble and anti-inflammatory and cheap. Here is some home work for you-
On the role of inflammation in PD-

1. Neurobiol Dis. 2010 Mar;37(3):510-8. Epub 2009 Nov 10.

Neuroinflammation in Parkinson's disease: its role in neuronal death and
implications for therapeutic intervention.

Tansey MG, Goldberg MS.

Department of Physiology, Emory University School of Medicine, 615 Michael
Street, Atlanta, GA 30324, USA. malu.tansey@emory.edu

Parkinson's disease (PD) is the second most common neurodegenerative disease,
after Alzheimer's disease. The potential causes of PD remain uncertain, but
recent studies suggest neuroinflammation and microglia activation play important
roles in PD pathogenesis. Major unanswered questions include whether protein
aggregates cause the selective loss of dopaminergic neurons in the substantia
nigra that underlies the clinical symptoms and whether neuroinflammation is a
consequence or a cause of nigral cell loss. Within the microenvironment of the
brain, glial cells play a critical role in homeostatic mechanisms that promote
neuronal survival. Microglia have a specialized immune surveillance role and
mediate innate immune responses to invading pathogens by secreting a myriad of
factors that include, cytokines, chemokines, prostaglandins, reactive oxygen and
nitrogen species, and growth factors. Some of these factors have neuroprotective
and trophic activities and aid in brain repair processes; while others enhance
oxidative stress and trigger apoptotic cascades in neurons. Therefore, pro- and
anti-inflammatory responses must be in balance to prevent the potential
detrimental effects of prolonged or unregulated inflammation-induced oxidative
stress on vulnerable neuronal populations. In this review, we discuss potential
triggers of neuroinflammation and review the strongest direct evidence that
chronic neuroinflammation may have a more important role to play in PD versus
other neurodegenerative diseases. Alternatively, we propose that genetic
deficiency is not the only way to reduce protective factors in the brain which
may function to keep microglial responses in check or regulate the sensitivity of
DA neurons. If chronic inflammation can be shown to decrease the levels of
neuroprotective factors in the midbrain, in essence genetic haploinsufficiency of
protective factors such as Parkin or RGS10 may result from purely environmental
triggers (aging, chronic systemic disease, etc.), increasing the vulnerability to
inflammation-induced nigral DA neuron death and predisposing an individual to
development of PD. Lastly, we review the latest epidemiological and experimental
evidence supporting the potential use of anti-inflammatory and immunomodulatory
drugs as neuroprotective agents to delay the progressive nigrostriatal
degeneration that leads to motor dysfunction in PD.

2009 Elsevier Inc. All rights reserved.

PMCID: PMC2823829
PMID: 19913097 [PubMed - indexed for MEDLINE]

Note: Free full text is available.

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1. Prog Neurobiol. 2009 Nov;89(3):277-87. Epub 2009 Aug 15.

The influence of microglia on the pathogenesis of Parkinson's disease.

Long-Smith CM, Sullivan AM, Nolan YM.

Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.

Parkinson's disease (PD) is characterised by degeneration of dopaminergic neurons
in the substantia nigra pars compacta (SNpc). Inflammation may be associated with
the neuropathology of PD due to the following accumulating evidence: excessive
microglial activation and increased levels of the pro-inflammatory cytokines
tumour necrosis factor-alpha and interleukin-1beta in the SNpc of patients with
PD; the emergence of PD-like symptoms following influenza infection; the
increased susceptibility to PD associated with bacterial vaginosis; the presence
of inflammatory mediators and activators in animal models of PD; the ability of
anti-inflammatory drugs to decrease susceptibility to PD; and the emerging
possibility of the use of microglial activation inhibitors as a therapy in PD. In
this review, we will discuss the role of inflammation in PD. We will focus on the
influence of microglia in the pathogenesis of PD and discuss potential
therapeutic interventions for PD, that target microglia.

PMID: 19686799 [PubMed - indexed for MEDLINE]

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1. Br J Pharmacol. 2007 Apr;150(8):963-76. Epub 2007 Mar 5.

Inflammation as a causative factor in the aetiology of Parkinson's disease.

Whitton PS.

1Department of Pharmacology, The School of Pharmacy, London, UK.
peter.whitton@pharmacy.ac.uk

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting
mainly the elderly, although a small proportion of PD patients develop the
illness at a much younger age. In the former group, idiopathic PD patients, the
causes of the illness have been the subject of longstanding debate with
environmental toxins, mitochondrial dysfunction, abnormal protein handling and
oxidative stress being suggested. One problem has been that the epidemiology of
PD has offered few clues to provide evidence for a single major causative factor.
Comparatively recently it has been found that in both patients and experimental
models of PD in animals neuroinflammation appears to be a ubiquitous finding.
These cases present with all of the classical features of inflammation including
phagocyte activation, increased synthesis and release of proinflammatory
cytokines and complement activation. Although this process is vital for normal
function and protection in both the CNS, as in the periphery, it is postulated
that in the aetiology of PD this process may spiral out of control with over
activation of microglia, over production of cytokines and other proinflammatory
mediators as well as the release of destructive molecules such as reactive oxygen
species. Given that dopaminergic neurons in the substantia nigra are relatively
vulnerable to 'stress' and the region has a large population of microglia in
comparison to other CNS structures, these events may easily trigger
neurodegeneration. These factors are examined in this review along with a
consideration of the possible use of anti-inflammatory drugs in PD.

PMCID: PMC2013918
PMID: 17339843 [PubMed - indexed for MEDLINE]

Full text available