Progress and Prospects in Parkinson's Research/Therapy/Neuroprotection/Minocycline
The results of tests on the neuroprotective qualities of minicycine to date are ambiguous.
Minocycline (INN) is a broad-spectrum tetracycline antibiotic,
Du et al  tested the neuroprotective properties of minocycline and found that;-
- It prevents nigrostriatal dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease.
- It also blocked dopamine depletion in the striatum as well as in the nucleus accumbens after MPTP administration.
Yang et al  measured the effect of minocycline on rats with Parkinsonism induced by MPTP.
We found that although minocycline inhibited microglial activation, it significantly exacerbated MPTP-induced damage to DA neurons. We present evidence suggesting that this effect may be due to inhibition of DA and 1-methyl-4-phenylpridium (MPP+) uptake into striatal vesicles.
Diguet et al  tried different doses of minocycline on Parkinsonian mice and monkeys with a range of results. Some improved and some worsened. Their conclusion:-
Minocycline may have variable and even deleterious effects in different species and models according to the mode of administration and dose.
NINDS NET-PD Investigators  Creatine and minocycline were prioritized for testing in Phase II clinical trials based on a systematic evaluation of potentially disease modifying compounds for Parkinson's disease.
The conclusion was that both creatine and minocycline should be considered for definitive Phase III trials to determine if they alter the long term progression of Parkinson's disease.
Quintero et al  observed the effects of treatment of 6-OHDA Parkinsonian rats with timed doses of minocycline. Their conclusions:-
These data suggest that the therapeutic potential of minocycline may depend on the time of drug administration relative to neuropathogenic event.
Faust et al  reported on a series of tests with fruit flies.
In the present study, a Drosophila DJ-1A model of PD was used to test potential neuroprotective drugs. The drugs applied are the Chinese herb celastrol, the antibiotic minocycline, the bioenergetic amine coenzyme Q10 (coQ10), and the glutamate antagonist 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo[f]-quinoxaline (NBQX). All of these drugs target pathogenic processes implicated in PD, thus constitute mechanism-based treatment strategies. We show that celastrol and minocycline, both having antioxidant and anti-inflammatory properties, confer potent dopaminergic neuroprotection in Drosophila DJ-1A model, while coQ10 shows no protective effect. NBQX exerts differential effects on cell survival and brain dopamine content: it protects against DN loss but fails to restore brain dopamine level.
Radad et al  Treated mice, who were rendered Parkinsonian with the application of rotenone, with minocycline. Their conclusions:-
Minocycline has neuroprotective potential against the progressive loss of tyrosine hydroxylase immunoreactive neurons induced by long-term rotenone toxicity in primary dopaminergic cultures.
Noble, Wendy; Garwood, Claire J. and Hanger, Diane P. Prion. Full Text 3 (2): 78–83.
Minocycline as a potential therapeutic agent in neurodegenerative disorders characterised by protein misfolding.
Plane, Jennier M.; Shen, Yan; David E. Pleasure, David E. and Deng, Wenbin. Full Text Arch. Neurol. 67 (12): 1442–1448.
Prospects for Minocycline Neuroprotection
Schildknecht, Stefan; Pape, Regina; Müller, Nathalie; Robotta, Marta; Andreas Marquardt, Andrea; Bürkle, Alexander: Drescher, Malte¶ and Leist, Marcel. Full Text J. Biol Chem. 286 (7): 4991–5002.
Neuroprotection by Minocycline Caused by Direct and Specific Scavenging of Peroxynitrite http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037611/?tool=pmcentrez
Use the following links to query the PubMed, PubMed Central and Google Scholar databases using the Search terms:- Parkinson's_Disease Minocyline.
This will list the latest papers on this topic. You are invited to update this page to reflect such recent results, pointing out their significance.
- Substances with possible neuroprotective properties:
- Caffeine,--Celastrol,--Co-Enzyme Q10,--Creatine,--DHA,--Exendin-4 (EX-4),--GDNF,--Glutathione (GSH),--GM1,--Isradipine,--Melatonin,--Minocycline,--Nicotine,--NSAIDs,--Phenylbutyrate,--Phytic Acid,--Probucol,--Quinoxaline,--Rasagiline,--Riboflavin,--Statins,--Tolcapone,--Urate & Uric Acid,--Vitamin D,--Vitamin E,--
- Du, Y.; Ma, Z.; Lin, S.; Dodel, R. C.; Gao, F,; Bales, K R.; Triarhou L. C.; Chernet, E.; Perry, K. W.; Nelson, D. L.; Luecke, S.; Phebus, L. A.; Bymaster, F. P.; Paul, S. M. (2001) Abstract Proc. Natl. Acad. Sci. U. S. A. 98 (25):14669 - 14674. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. http://www.ncbi.nlm.nih.gov/pubmed/11724929
- Yang, L.; Sugama, S,; Chirichigno, J. W.; Gregorio, J.; Lorenzl, S.; Shin, D. H.; Browne, S. E.; Shimizu, Y.; Joh, T. H.; Beal, M. F. and Albers, D. S.(2003) Abstract J. Neurosci. Res. 74 (2):278 - 285. Minocycline enhances MPTP toxicity to dopaminergic neurons. http://www.ncbi.nlm.nih.gov/pubmed/14515357
- Diguet, E.; Fernagut, P. O.; Wei, X.; Du, Y.;; Rouland, R.; Gross. C.; Bezard, E. and Tison, F.(2004) Abstract Eur. J. Neurosci. 19 (12):3266 - 3276. Deleterious effects of minocycline in animal models of Parkinson's disease and Huntington's disease. http://www.ncbi.nlm.nih.gov/pubmed/15217383
- NINDS NET-PD Investigators (2006)Abstract Neurology. 66 (5):664 - 671. A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson's disease. http://www.ncbi.nlm.nih.gov/pubmed/16481597
- Quintero, E. M.; Willis L.; Singleton, R.; Harris, N.; Huang, P.; Bhat, N. and Granholm, A. C. (2006) Abstract Brain Res. 1093 (1):198 - 207. Behavioral and morphological effects of minocycline in the 6-hydroxydopamine rat model of Parkinson's disease. http://www.ncbi.nlm.nih.gov/pubmed/16712819
- Faust, K,; Gehrke, S.; Yang, Y.; Yang, L.; Beal M. F. and Lu, B.(2009)Abstract BMC Neurosci. Sep 1;10:109. Neuroprotective effects of compounds with antioxidant and anti-inflammatory properties in a Drosophila model of Parkinson's disease. http://www.ncbi.nlm.nih.gov/pubmed/19723328
- Radad, K.; Moldzio, R. and Rausch, W. D. (2010) Abstract Can. J. Neurol. Sci. 37 (1):81 - 85. Minocycline protects dopaminergic neurons against long term rotenone toxicity. http://www.ncbi.nlm.nih.gov/pubmed/20169778