Glia: Initiators and progressors of pathology in Parkinson's disease

Halliday, Glenda M.; Stevens, Claire H.

doi:10.1002/mds.23455

Cited by 395 publications

(387 citation statements)

References 136 publications

(166 reference statements)

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“…Activation of both, microglia and astroglia is seen in animal models of PD and they are considered active participants in the nigrostriatal degeneration (Halliday and Stevens, 2011;Mena and Garcia de, 2008;Teismann and Schulz, 2004;Wu et al, 2002). Yet, in the brain parenchyma astrocytes are responsible for creating and maintaining an environment that optimizes neuronal function (Barres, 2008;Episcopo et al, 2013;Hertz and Zielke, 2004;Hirrlinger and Dringen, 2010;Kimelberg, 2010;Volterra and Meldolesi, 2005).…”

Section: Midbrain Astroglia Responsesmentioning

confidence: 99%

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Sikorska

Lanthier

Miller

et al. 2014

Neurobiology of Aging

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Although the support for the use of antioxidants, such as coenzyme Q 10 (CoQ 10 ), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ 10 is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ 10 (Ubisol-Q 10 ) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q 10 was delivered in drinking water. Prophylactic application of Ubisol-Q 10 , started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q 10 group by day 28). Therapeutic application of Ubisol-Q 10 , given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q 10 concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ 10 /kg body weight/day, showing clearly that high doses of CoQ 10 were not required to deliver these effects. Furthermore, the Ubisol-Q 10 treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q 10 was capable of halting the neurodegeneration already in progress;

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Section: Midbrain Astroglia Responsesmentioning

confidence: 99%

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Sikorska

Lanthier

Miller

et al. 2014

Neurobiology of Aging

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“…Previous authors have demonstrated the pathogenetic role of activated microglia and the resulted neuroinflammation in both Alzheimer's and Parkinson's disease [3,5,6,71].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have revealed that α-synuclein's misfolded deposits act as an inflammatory stimulator of microglia, which is further escalated by the production of superoxide anions and other neurotoxic factors (TNF-α, chemokines and autoantibodies), including anti-ganglioside antibodies [2][3][4][5][6]. However, according to other issues gangliosides seem to restrain the pathological aggregation of α-synuclein [7].…”

Section: Introductionmentioning

confidence: 99%

High Levels of Anti-Ganglioside Antibodies in Patients with Parkinson?s Disease Associated with Cognitive Decline

M¹

2015

Int J Neurorehabilitation Eng

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“…reactive microgliosis, are currently believed to be actively involved in the pathogenesis of various neurodegenerative diseases including PD, AD, multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) (Gao & Hong, 2008;Glass et al, 2010;Kim & Joh, 2006;Long-Smith et al, 2009). At present, whether microglial activation ultimately protects or actually exacerbates neuronal loss in the context of PD and other related diseases is still under debate (Delgado & Ganea, 2003;Gao & Hong, 2008;Halliday & Stevens, 2011;Sanchez-Pernaute et al, 2004;Vila et al, 2001;Wu et al, 2002;Wyss-Coray & Mucke, 2002), although the current view favours the second hypothesis. Evidence of microglial attack in PD is supported by findings from epidemiological studies, animal models, and cell culture experiments (McGeer & McGeer, 2008).…”

Section: Neuroinflammation In Pdmentioning

confidence: 96%

“…Together with microglial cells, astrocytes and oligodendrocytes are part of glia, which normally serve neuroprotective functions but, given adverse stimulation as discussed before, they may contribute to develop chronic neuroinflammation (Halliday & Stevens, 2011;McGeer & McGeer, 2008). Compared to microglia, the functions of astrocytes are poorly understood.…”

Section: Links Between Syn and Astrocytes And Oligodendrocytesmentioning

confidence: 99%