Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation, Phagocytosis and Dopaminergic Degeneration in MPTP-Treated Mice

Costa, T.R.; Fernández-Villalba, Emiliano; Izura, Virginia; Lucas-Ochoa, A M; Menezes-Filho, Noelio J.; Santana, Rejane Conceição; Oliveira, Marco de; Araújo, F.; Estrada, Cristina; Silva, Vda; Costa, Sílvia Lima; Herrero, María Teófila Vicente

doi:10.1007/s11481-020-09925-8

Cited by 33 publications

(26 citation statements)

References 63 publications

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“…This localised microgliosis is also present in the MPTP mouse model of PD ( 84 ), the A53T α-syn transgenic mouse model of PD following administration of LPS ( 85 ) and the L-dopa-induced dyskinesia rat model of PD ( 86 ). Blocking microglial activation with a combination of matrix metalloproteinase inhibitor 1-DNJ plus ibuprofen is protective against dopamine neuronal loss ( 87 ) suggesting that microglia are key contributors to PD pathology.…”

Section: Microglia and Their Role In Parkinson's Diseasementioning

confidence: 99%

The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?

et al. 2021

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Parkinson's disease (PD), the second most common neurodegenerative disease, is characterised by the motor symptoms of bradykinesia, rigidity and resting tremor and non-motor symptoms of sleep disturbances, constipation, and depression. Pathological hallmarks include neuroinflammation, degeneration of dopaminergic neurons in the substantia nigra pars compacta, and accumulation of misfolded α-synuclein proteins as intra-cytoplasmic Lewy bodies and neurites. Microglia and astrocytes are essential to maintaining homeostasis within the central nervous system (CNS), including providing protection through the process of gliosis. However, dysregulation of glial cells results in disruption of homeostasis leading to a chronic pro-inflammatory, deleterious environment, implicated in numerous CNS diseases. Recent evidence has demonstrated a role for peripheral immune cells, in particular T lymphocytes in the pathogenesis of PD. These cells infiltrate the CNS, and accumulate in the substantia nigra, where they secrete pro-inflammatory cytokines, stimulate surrounding immune cells, and induce dopaminergic neuronal cell death. Indeed, a greater understanding of the integrated network of communication that exists between glial cells and peripheral immune cells may increase our understanding of disease pathogenesis and hence provide novel therapeutic approaches.

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Section: Microglia and Their Role In Parkinson's Diseasementioning

confidence: 99%

The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?

et al. 2021

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“…Moreover, it has been stated that ibuprofen individually raised the quantity of DArgic nerve cells by approximately 47% [ 180 ]. A recent study has reported that multimodal therapy with an iminosugar, namely 1-deoxynojirimycin (1-DNJ) and a NSAID, namely ibuprofen, impedes destruction of mesencephalic DArgic nerve cells, minimizes the levels of inflammatory mediators like interleukin-6 (IL-6) and TNF-α, total microglia markers namely CD68 + /Iba-1 + cells, and interaction between microglia cells and nerve cells in MPTP-subjected experimental mice model [ 182 ].…”

Section: Experimental Studies Portraying the Deep Insights Into The Neuroprotective Role Of Ppar Agonists In Pdmentioning

confidence: 99%

Elucidating the Neuroprotective Role of PPARs in Parkinson’s Disease: A Neoteric and Prospective Target

Behl

Madaan

Sehgal

et al. 2021

IJMS

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One of the utmost frequently emerging neurodegenerative diseases, Parkinson’s disease (PD) must be comprehended through the forfeit of dopamine (DA)-generating nerve cells in the substantia nigra pars compacta (SN-PC). The etiology and pathogenesis underlying the emergence of PD is still obscure. However, expanding corroboration encourages the involvement of genetic and environmental factors in the etiology of PD. The destruction of numerous cellular components, namely oxidative stress, ubiquitin-proteasome system (UPS) dysfunction, autophagy-lysosome system dysfunction, neuroinflammation and programmed cell death, and mitochondrial dysfunction partake in the pathogenesis of PD. Present-day pharmacotherapy can alleviate the manifestations, but no therapy has been demonstrated to cease disease progression. Peroxisome proliferator-activated receptors (PPARs) are ligand-directed transcription factors pertaining to the class of nuclear hormone receptors (NHR), and are implicated in the modulation of mitochondrial operation, inflammation, wound healing, redox equilibrium, and metabolism of blood sugar and lipids. Numerous PPAR agonists have been recognized to safeguard nerve cells from oxidative destruction, inflammation, and programmed cell death in PD and other neurodegenerative diseases. Additionally, various investigations suggest that regular administration of PPAR-activating non-steroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, indomethacin), and leukotriene receptor antagonists (montelukast) were related to the de-escalated evolution of neurodegenerative diseases. The present review elucidates the emerging evidence enlightening the neuroprotective outcomes of PPAR agonists in in vivo and in vitro models experiencing PD. Existing articles up to the present were procured through PubMed, MEDLINE, etc., utilizing specific keywords spotlighted in this review. Furthermore, the authors aim to provide insight into the neuroprotective actions of PPAR agonists by outlining the pharmacological mechanism. As a conclusion, PPAR agonists exhibit neuroprotection through modulating the expression of a group of genes implicated in cellular survival pathways, and may be a propitious target in the therapy of incapacitating neurodegenerative diseases like PD.

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“…BCLAF1 was used here to validate the efficacy of miR-142-3p mimic. Alongside with its effect on BCLAF1 expression, miR-142-3p overexpression also influenced HMC3 activation state as assessed by increased CD68 level ( Figure 5D , right panel), a marker of microglia activation [ 25 , 26 ]. Interestingly, VEGF-A transcript level ( Figure 5E , right panel) increased upon miR-142-3p mimic, which could contribute to the effect observed in vivo on the angiogenic response.…”

Section: Resultsmentioning

confidence: 99%

“…Besides morphological analysis, future studies may evaluate mouse microglia activation state through transcriptomic and surface marker analyses. Interestingly, in human microglia culture, miR-142-3p mimic enhanced drastically miR-142-3p levels, as well as CD68 expression, a marker of activated microglia [ 25 , 26 ]. An interesting finding is the concomitant up-regulation of VEGF-A, a key molecular mediator of CNV progression [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Intravitreal injection of anti-miRs against miR-142-3p reduces angiogenesis and microglia activation in a mouse model of laser-induced choroidal neovascularization

Roblain

Louis

Yip

et al. 2021

Aging

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Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation, Phagocytosis and Dopaminergic Degeneration in MPTP-Treated Mice

Cited by 33 publications

References 63 publications

The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?

The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?

Elucidating the Neuroprotective Role of PPARs in Parkinson’s Disease: A Neoteric and Prospective Target

Intravitreal injection of anti-miRs against miR-142-3p reduces angiogenesis and microglia activation in a mouse model of laser-induced choroidal neovascularization

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