Mitochondrial dysfunction: A potential link between neuroinflammation and neurodegeneration?

Witte, Maarten E.; Geurts, Jeroen J. G.; Vries, Helga E. de; Valk, Paul van der; Horssen, Jack van

doi:10.1016/j.mito.2010.05.014

Cited by 208 publications

(130 citation statements)

References 138 publications

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“…A role for inflammation in mitochondrial dysfunction is suggested by post-mortem studies showing that reactive oxygen species (ROS) produced by activated microglia and macrophages can induce mitochondrial dysfunction not only in the white matter 120 , but also in the grey matter lesions 104 . Several lines of evidence have led to the hypothesis that mitochondrial injury is a primary phenomenon in multiple sclerosis 121 .…”

Section: Box 2: Role Of Mitochondrial Injury In Grey Matter Damagementioning

confidence: 99%

Exploring the origins of grey matter damage in multiple sclerosis

et al. 2015

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Multiple sclerosis is characterized at the gross pathological level by the presence of widespread focal demyelinating lesions of the myelin-rich white matter. However, it is becoming clear that grey matter is not spared, even during the earliest phases of the disease. Furthermore, grey matter damage may have an important role both in physical and cognitive disability. Grey matter pathology involves both inflammatory and neurodegenerative mechanisms, but the relationship between the two is unclear. Histological, immunological and neuroimaging studies have provided new insight in this rapidly expanding field, and form the basis of the most recent hypotheses on the pathogenesis of grey matter damage. DOI: https://doi.org/10.1038/nrn3900Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-111099 Accepted Version Originally published at: Calabrese, Massimiliano; Magliozzi, Roberta; Ciccarelli, Olga; Geurts, Jeroen J G; Reynolds, Richard; Martin, Roland (2015). Exploring the origins of grey matter damage in multiple sclerosis. Nature Reviews Neuroscience, 16 (3) AbstractMultiple sclerosis is characterised at the gross pathological level by the presence of widespread focal demyelinating lesions of the myelin-rich white matter. However, in recent years it has become clear that grey matter is not spared, even during the earliest phases of the disease. Furthermore, grey matter damage has been suggested to have an important role both in physical and cognitive disability. Grey matter pathology involves both inflammatory and neurodegenerative mechanisms, but the relationship between the two is unclear. This review will summarize and highlight important histological, immunological, and neuroimaging results from this rapidly expanding field and will address the most recent hypotheses on the pathogenesis of grey matter damage.

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Section: Box 2: Role Of Mitochondrial Injury In Grey Matter Damagementioning

confidence: 99%

Exploring the origins of grey matter damage in multiple sclerosis

et al. 2015

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“…2,18,23 Oxidative stress has been strongly suggested to play an important role in the early, active phase of MS and also to contribute to neurodegeneration in the later stages. 2,10 Interestingly, a genetically determined ability to remove toxic products of oxidative stress, namely through GSTs-catalyzed reactions, has been shown to influence the long-term prognosis in MS. 26 The authors reported that polymorphisms in the GSTs of the class mu (GSTM) and class pi (GSTP), such as the GSTM3 AA genotype and homozygosity for both the GSTM1*0 and GSTP1*Ile105-containing allele are associated with more severe disability in patients with a disease duration of more than 10 years. 26 In fact, GSTP polymorphisms can affect substrate selectivity and stability, thereby increasing individual susceptibility; and individuals with the GSTP1*B allele have lower GSTP enzyme activity, thus displaying less efficient detoxification capacity.…”

Section: Glutathione Metabolism Dysfunction In Msmentioning

confidence: 99%

“…10 Dysfunctional mitochondria were recently shown to be implicated in both early and chronic stages of MS pathology, actively contributing to both axonal and neuronal injury. [11][12][13] The cause of mitochondrial dysfunction in patients with MS has been debated, but evidence is emerging that ROS production by macrophages/microglia might induce mitochondrial dysfunction in patients with MS, 10,13 possibly via oxidative damage to mitochondrial DNA. 12 Oxidative damage contribution to MS lesion formation In the initial phase of MS lesion formation, locally produced ROS can induce blood-brain barrier (BBB) disruption and promote leukocyte migration.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, mitochondrial dysfunction in the cortical neurons of progressive MS patients is extensive and likely to contribute to the ongoing oxidative stress in advanced stages of the disease. 10,13 Given the susceptibility of the CNS to ROS, it is conceivable that oxidative stress significantly contributes to neurodegeneration in progressive MS.…”

Section: Introductionmentioning

confidence: 99%

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Glutathione in multiple sclerosis: More than just an antioxidant?

et al. 2014

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Abstract:Oxidative stress has been strongly implicated in both the inflammatory and neurodegenerative pathological mechanisms in multiple sclerosis (MS). In response to oxidative stress, cells increase and activate their cellular antioxidant mechanisms. Glutathione (GSH) is the major antioxidant in the brain, and as such plays a pivotal role in the detoxification of reactive oxidants. Previous research has shown that GSH homeostasis is altered in MS. In this review, we provide a comprehensive overview on GSH metabolism in brain cells, with a focus on its involvement in MS. The potential of GSH as an in vivo biomarker in MS is discussed, along with a short overview of improvements in imaging methods that allow non-invasive quantification of GSH in the brain. These methods might be instrumental in providing realtime measures of GSH, allowing the assessment of the oxidative state in MS patients and the monitoring of disease progression. Finally, the therapeutic potential of GSH in MS is discussed.

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“…Neuroinflamação tem sido um alvo de investigação como um mecanismo implicado na neuroprogressão 2,19 ; algumas citocinas provenientes de células residentes e provenientes da periferia têm a capacidade de causar toxicidade e apoptose em neurônios e células da glia 88,89 16 . Um dos alvos de pesquisa primários tem sido o TNF-a 87 .…”

Section: Mediadores Inflamatóriosunclassified

Marcadores periféricos e a fisiopatologia do transtorno bipolar

Magalhães¹,

Fries²,

Kapczinski³

2012

Rev. psiquiatr. clín.

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Introdução: O entendimento da fisiopatologia do transtorno bipolar vem tendo avanços consistentes nos últimos anos. Um enfoque na relação entre carga alostática e alterações sistêmicas vem tomando corpo, com o objetivo de se entender a frequente progressão da doença. Proeminentes entre os mediadores periféricos têm sido as moléculas que poderiam ser amplamente agrupadas em neurotrofinas, marcadores de estresse oxidativo e marcadores inflamatórios. Objetivo: Descrever achados recentes em relação à fisiopatologia sistêmica do transtorno bipolar, com enfoque especial em estudos brasileiros, tentando articular uma visão coerente do conhecimento atual do campo. Método: Revisão narrativa da literatura relacionada a neurotrofinas, estresse oxidativo e marcadores inflamatórios no transtorno bipolar. Resultados: Diversas fontes de evidência, provenientes tanto de estudos pré-clínicos quanto clínicos, revelam consistentemente alterações sistêmicas no transtorno bipolar. Os achados são especialmente robustos em pacientes com múltiplos episódios. Nesses, alterações relacionadas a episódios de mania e depressão são notáveis em neurotrofinas e dano oxidativo a lipídeos. Um número menor de estudos mostra alterações no sistema imune, em particular estados pró-inflamatórios. Conclusão: Alterações sistêmicas que correlacionam o transtorno bipolar a comorbidade clínica, disfunção cognitiva, incapacidade e mortalidade precoce começam a ser traçadas. Estudos envolvendo desenhos longitudinais, amostras populacionais e ensaios clínicos envolvendo marcadores periféricos devem ser incorporados no futuro próximo e reforçar a validade de uma noção de envolvimento multissistêmico no transtorno bipolar.Magalhães PVS, et al. / Rev Psiq Clín. 2012;39(2):60-7 Palavras-chave: Transtorno bipolar, inflamação, estresse oxidativo, neurotrofinas, fator neurotrófico derivado do cérebro, fisiopatologia, biomarcadores. ABSTRACT Introduction:The understanding of the pathophysiology of bipolar disorder has steadily advanced in the past few years. Thereby, a focus on allostatic load and systemic changes has appeared, with the aim to understand illness progression. Amongst the peripheral markers, molecules that can be widely classified into neurotrophins, oxidadive stress markers, and inflammation markers have been elevated. Objective: To describe recent findings regarding the systemic pathophysiology of bipolar disorder, with a special focus on Brazilian studies and to create a coherent view of the current knowledge in the field. Method: Narrative review of the literature regarding neurotrophins, oxidative stress, and inflammatory markers in bipolar disorder. Results: A diverse body of evidence, based on both pre-clinical and clinical studies, reveals consistent systemic changes in bipolar disorder. The findings are particularly robust in patients after multiple episodes. Thereby, remarkable changes related to manic and depressive episodes were found in neurotrophins and oxidative damage to lipids. Regarding to immune system alterations, in particular pro...

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Mitochondrial dysfunction: A potential link between neuroinflammation and neurodegeneration?

Cited by 208 publications

References 138 publications

Exploring the origins of grey matter damage in multiple sclerosis

Exploring the origins of grey matter damage in multiple sclerosis

Glutathione in multiple sclerosis: More than just an antioxidant?

Marcadores periféricos e a fisiopatologia do transtorno bipolar

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