Pathologische Anatomie und Pathogenese

Müller, Eduard

doi:10.1007/978-3-642-50921-6_3

Cited by 5 publications

(3 citation statements)

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“…Indeed, glial cells and astrocytes, in particular, were found to be highly abnormal, early in the study of MS lesions ( 11 ). Large and bizarre astrocytes containing multiple and sometimes fragmented nuclei or engulfing other cells were found in early active lesions ( 12 ), and considered by investigators during the late nineteenth and early twentieth century, to be the major cell type targeted in MS ( 13 ). However, later identification of oligodendrocytes as the myelinating cell of the CNS, as well as of their depletion from MS lesions, caused the role of astrocytes in MS pathogenesis to be largely ignored after about 1930.…”

Section: Introductionmentioning

confidence: 99%

The Role of Astrocytes in Multiple Sclerosis Progression

2015

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Multiple sclerosis (MS) is an inflammatory disorder causing central nervous system (CNS) demyelination and axonal injury. Although its etiology remains elusive, several lines of evidence support the concept that autoimmunity plays a major role in disease pathogenesis. The course of MS is highly variable; nevertheless, the majority of patients initially present a relapsing–remitting clinical course. After 10–15 years of disease, this pattern becomes progressive in up to 50% of untreated patients, during which time clinical symptoms slowly cause constant deterioration over a period of many years. In about 15% of MS patients, however, disease progression is relentless from disease onset. Published evidence supports the concept that progressive MS reflects a poorly understood mechanism of insidious axonal degeneration and neuronal loss. Recently, the type of microglial cell and of astrocyte activation and proliferation observed has suggested contribution of resident CNS cells may play a critical role in disease progression. Astrocytes could contribute to this process through several mechanisms: (a) as part of the innate immune system, (b) as a source of cytotoxic factors, (c) inhibiting remyelination and axonal regeneration by forming a glial scar, and (d) contributing to axonal mitochondrial dysfunction. Furthermore, regulatory mechanisms mediated by astrocytes can be affected by aging. Notably, astrocytes might also limit the detrimental effects of pro-inflammatory factors, while providing support and protection for oligodendrocytes and neurons. Because of the dichotomy observed in astrocytic effects, the design of therapeutic strategies targeting astrocytes becomes a challenging endeavor. Better knowledge of molecular and functional properties of astrocytes, therefore, should promote understanding of their specific role in MS pathophysiology, and consequently lead to development of novel and more successful therapeutic approaches.

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Section: Introductionmentioning

confidence: 99%

The Role of Astrocytes in Multiple Sclerosis Progression

2015

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“…Others have also shown that astrocytes can modulate myelination. Indeed, in 1904 it was proposed that hypertrophic/reactive astrocytes were a pathological feature of multiple sclerosis (MS), and it was hypothesised that they had an important role in the disease (Müller, 1904). A similar hypothesis was raised by Wu & Raine (1992) from studies of human MS lesions.…”

Section: Introductionmentioning

confidence: 99%

Astrocyte phenotypes and their relationship to myelination

2010

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Astrocytes are one of the major glial cell types that maintain homeostasis in the undamaged CNS. After injury and disease, astrocytes become reactive and prevent regeneration; however, it has also been suggested that astrocytes can become activated and promote regeneration. Thus, it is hypothesised that astrocytes have an important role in modulating CNS repair. This review will focus on the variable phenotypic state of astrocytes that range from inactive ⁄ quiescent to reactive, and relate these to their ability to influence myelination. Using myelinating cultures plated on astrocytes we propose a possible mechanism for oligodendrocyte precursor cell interaction with the axon, leading to myelination. The phenotypic status of astrocytes is an intriguing and widely discussed issue, which is critical for understanding the mechanisms involved in CNS injury and its subsequent repair.

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“…As early as 1904, it was suggested that MS was a disease of astrocytes (Müller 1904), and although this concept is no longer believed to hold for MS itself, it is now clear astrocytes are the primary pathological target in a number of rare genetic and autoimmune diseases (reviewed by Sofroniew and Vinters 2010). Alexander disease is a fatal neurodegenerative condition that involves the destruction of myelin and is caused by mutations in Gfap (Brenner and others 2001).…”

Section: Astrocytes As Pathological Targets In Neurological Diseasesmentioning

confidence: 99%

Myelination

Barnett

Linington

2012

Neuroscientist

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Astrocytes are the most abundant cell type in the adult central nervous system (CNS), and their functional diversity in response to injury is now being appreciated. Astrocytes have long been considered the main player in the inhibition of CNS repair via the formation of the gliotic scar, but now it is accepted that astrocyte can play an important role in CNS repair and remyelination. Interest in the relationship between astrocytes and myelination focused initially on attempts to understand how the development of plaques of astroglial scar tissue in multiple sclerosis was related to the failure of these lesions to remyelinate. It is now considered that this is an end stage pathological response to injury, and that normally astrocytes play important roles in supporting the development and maintenance of CNS myelin. This review will focus on how this new understanding may be exploited to develop new strategies to enhance remyelination in multiple sclerosis and other diseases.

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Pathologische Anatomie und Pathogenese

Cited by 5 publications

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The Role of Astrocytes in Multiple Sclerosis Progression

The Role of Astrocytes in Multiple Sclerosis Progression

Astrocyte phenotypes and their relationship to myelination

Myelination

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