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Minocycline: Neuroprotective Mechanisms in Parkinsons Disease
Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by cardinal features of tremor, bradykinesia, rigidity and postural instability. In addition to the motor symptoms patients experience cognitive decline eventually resulting in severe disability. Pathologically PD is characterized by neurodegeneration in the substantia nigra pars compacta (SNc) with intracytoplasmic inclusions known as Lewy bodies. In addition to the SNc there is neurodegeneration in other areas including cerebral cortex, raphe nuclei, locus ceruleus, nucleus basalis of meynert, cranial nerves and autonomic nervous system. Recent evidence supports the role of inflammation in Parkinson's disease. Apoptosis has been shown to be one of the pathways of cell death in PD. Minocycline, a tetracycline derivative is a caspase inhibitor, and also inhibits the inducible nitric oxide synthase which are important for apoptotic cell death. Furthermore, Minocycline has been shown to block microglial activation of 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonism animal models and protect against nigrostriatal dopaminergic neurodegeneration. In this review, we present the current experimental evidence for the potential use of tetracycline derivative, minocycline, as a neuroprotective agent in PD.
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“Thanks to the ability to efficiently cross the BBB, minocycline is considered neuroprotective for a variety of neurological conditions, including PD [251,252,253,254,255,256,257].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [256]
In the citing paper
“Thanks to the ability to efficiently cross the BBB, minocycline is considered neuroprotective for a variety of neurological conditions, including PD [251,252,253,254,255,256,257].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [256]
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Tetracyclines for neurodegenerative disorders, what about Pentacyclines specifically?Preprint
Damavandi, P. T. (2021) · doi:10.31219/osf.io/3csn4
Burn-induced distant organ ınjury in rats and the effect of minocycline
BAHADIR, E., Sancar, M., TARHAN, G. G., KOÇAK, E., BUDANCAMANAK, Z., Karaaslan, S., Demirci, E., Yüksel, M., Ercan, F., & Ali̇can, İ. (2017) · Marmara medical journal · doi:10.5472/marumj.357247
Penicillins, cephalosporins, other beta-lactam antibiotics, and tetracyclines
Midtvedt, T. (2005) · Side effects of drugs annual · doi:10.1016/s0378-6080(05)80447-7
(2010) · Elsevier eBooks · doi:10.1016/b978-0-444-53272-5.50005-4
Schmidt, E. K. A., Raposo, P. J. F., Espin, A. T., Fenrich, K. K., & Fouad, K. (2021) · Figshare · doi:10.6084/m9.figshare.14853219
Schmidt, E. K. A., Raposo, P. J. F., Espin, A. T., Fenrich, K. K., & Fouad, K. (2021) · Figshare · doi:10.6084/m9.figshare.14853213
Schmidt, E. K. A., Raposo, P. J. F., Espin, A. T., Fenrich, K. K., & Fouad, K. (2021) · Figshare · doi:10.6084/m9.figshare.14853225
Schmidt, E. K. A., Raposo, P. J. F., Espin, A. T., Fenrich, K. K., & Fouad, K. (2021) · Figshare · doi:10.6084/m9.figshare.14853204
Schmidt, E. K. A., Raposo, P. J. F., Espin, A. T., Fenrich, K. K., & Fouad, K. (2021) · Figshare · doi:10.6084/m9.figshare.14853210
Schmidt, E. K. A., Raposo, P. J. F., Espin, A. T., Fenrich, K. K., & Fouad, K. (2021) · Figshare · doi:10.6084/m9.figshare.14853222
Schmidt, E. K. A., Raposo, P. J. F., Espin, A. T., Fenrich, K. K., & Fouad, K. (2021) · Figshare · doi:10.6084/m9.figshare.14853207
Schmidt, E. K. A., Raposo, P. J. F., Espin, A. T., Fenrich, K. K., & Fouad, K. (2021) · Figshare · doi:10.6084/m9.figshare.14853201
Schmidt, E. K. A., Raposo, P. J. F., Espin, A. T., Fenrich, K. K., & Fouad, K. (2021) · Figshare · doi:10.6084/m9.figshare.14853216
Repurposing of doxycycline as a novel therapeutic avenue for management of parkinson’s disease
Ali, N. H., Al-Kuraishy, H. M., Hussain, N. R., Al-Gareeb, A. I., Albuhadily, A. K., Waheeb, T. S., & Batiha, G. E. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02156-y
“…underlying mechanisms of the neuroprotective effect of minocycline are unclear, it is reasonable to assume that minocycline might exert its effect through an interactive sig - naling network including the mitochondria, oxidative stress, excitotoxicity, PARP-1, and apoptosis (Thomas et al. 2004).”
Metadata
- Authors
- Thomas, M., & Le, W.
- Affiliations
- Baylor College of Medicine (US)
- Houston Methodist (US)
- Venue
- Current Pharmaceutical Design
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2004-02-01
- Volume
- 10
- Issue
- 6
- Pages
- 679-686
- ISSN
- 1381-6128 (ISSN-L)
- OpenAlex
- W2091324444
- Cited by
- 114
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 14 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 6 · 2015: 5 · 2014: 7 · 2013: 3 · 2012: 2
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Pharmaceutical Design (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (1R01 NS04367, R01NS040370, 1R01 NS40370)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- minocycline, Parkinson's disease, neuroprotection, neuroinflammation, apoptosis, caspase inhibition, inducible nitric oxide synthase, microglial activation, dopaminergic neuron loss, substantia nigra pars compacta, Lewy bodies, 6-hydroxydopamine, MPTP, tetracycline derivatives
- MeSH terms
- Animals, Antiparkinson Agents, Clinical Trials as Topic, Humans, Minocycline, Mitochondria, Parkinson Disease, Apoptosis, Oxidative Stress, Neuroprotective Agents
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