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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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Inflammation in neurodegenerative diseases
Amor, S., Puentes, F., Baker, D., & Van Der Valk, P. (2010) · Immunology · doi:10.1111/j.1365-2567.2009.03225.x · Cited by 1,355
Minocycline: Far beyond an Antibiotic
Garrido‐Mesa, N., Zarzuelo, A., & Gálvez, J. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12139 · Cited by 935
“The potential efficacy of minocycline in the treatment of Parkinson’s, Alzheimer’s and Huntington’s diseases has been proposed.”
BackgroundInfluentialMechanisms of noise-induced hearing loss indicate multiple methods of prevention
Prell, C. G. L., Yamashita, D., Minami, S., Yamasoba, T., & Miller, J. M. (2006) · Hearing Research · doi:10.1016/j.heares.2006.10.006 · Cited by 374
“…to play major roles in neurodegenerative diseases, such as Alzheimer’s disease (de la Monte et al., 2000;Gilgun-Sherki et al., 2003;Chong et al., 2004;Summers, 2004), Parkinson’s disease (Le and Frim, 2002;Tenenbaum et al., 2002;Thomas and Le, 2004), and traumatic brain injury (Lewen et al., 2000).”
BackgroundMicroglial phenotypes in Parkinson’s disease and animal models of the disease
Joers, V., Tansey, M. G., Mulas, G., & Carta, A. R. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.04.006 · Cited by 285
“Besides antimicrobial effects, minocycline was shown to exert neuroprotective and antiinflammatory activity in preclinical studies in the MPTP model of PD (Du et al., 2001; Thomas and Le, 2004; Wu et al., 2002).”
BackgroundThe mitochondrial death pathway: a promising therapeutic target in diseases
Gupta, S., Kass, G. E. N., Szegezdi, É., & Joseph, B. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00697.x · Cited by 283
“The semi-synthetic tetracycline antibiotic minocycline has been found in a large number of studies to provide protection from neurodegeneration and ischemic neuronal injury [338], CD95mediated hepatic injury [131] and hypoxic/ischemic renal and hepatic injury [310, 339].”
Background
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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