About this Research Topic
Multiple sclerosis (MS) is typically described as an autoimmune-driven chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). Still, its etiopathogenesis is elusive and being discussed.
It was thought that MS was caused by a dysregulated autoimmune attack of CD4+ T lymphocytes against myelin. This vision named outside-in paradigm. Recently it has been challenged by a complementary inside-out theory. According to the latter, the autoimmune activation represents a secondary reaction to a primary degenerative process occurring in the CNS. Conceptually, this causes myelin instability and disintegration that is followed, only in second instance, by a massive immunological activation to clear up the debris. Our aim is to collect the state-of-the-art of the current knowledge in the field. We would like to highlight which of the two hypotheses describes more accurately the mechanism involved in MS trigger.
The majority of the pathological observations can be equally described by both theories due to the heterogeneity of clinical manifestations and the technical difficulties in dissecting the triggering mechanisms.
Hence, a hot topic in the field is now to clarify which comes first: (auto)immunity or degeneration? Determining MS onset mechanisms might have a tremendous impact on disease prevention and management, thanks to the identification of new potential targets.
In this Research Topic, we aim to provide a translational contribution to the ongoing active discussion on the MS causes. Starting from the current knowledge supporting either autoimmune or neurodegenerative diseases towards an epidemiological and genetic focus that could also contribute to unravel MS etiopathogenesis.
The Topic is designed in a way that Opinion/(mini)Review articles are primarily constituting the core of the project. Original research and technical articles falling into the different subtopics of our issue are also warmly welcomed. To this aim, we will consider contributions coming from different disciplines (e.g. immunology, neuropathology, clinical neuroscience, neuroimaging, etc..) and focusing on one of the following:
1. Evidence of a primary CNS vs. immune system involvement as the main cause of MS etiopathogenesis;
2. Conventional (e.g. EAE) vs. unconventional/new (e.g. cuprizone, transgenic) animal models of MS;
3. Molecular pathways explaining MS etiopathogenesis as an outside-in or an inside-out mechanism;
4. Knowledge from other diseases affecting the CNS and mainly having a neurodegenerative (e.g., Alzheimer disease, Parkinson disease, etc.) and/or autoimmune (e.g. neuromyelitis optica spectrum disorders, anti-myelin oligodendrocyte glycoprotein syndrome, other inflammatory CNS disorders) etiopathogenesis to better understand the causes of MS;
5. The role of innate and adaptive immune system following an outside-in vs. inside-out approach: B-cells, T-cells, macrophages, and microglia;
6. Genetic and environmental factors in support or against the two different theories of MS etiopathogenesis;
7. How recent technical developments (e.g., laboratory, neuroimaging, etc.) could contribute to the identification of MS causes.
Topic Editor Paolo Preziosa received speaker honoraria from Biogen Idec, Novartis, Merck Serono and ExceMED. The rest of Topic Editors declare no competing interests with regards to the Research Topic.
It was thought that MS was caused by a dysregulated autoimmune attack of CD4+ T lymphocytes against myelin. This vision named outside-in paradigm. Recently it has been challenged by a complementary inside-out theory. According to the latter, the autoimmune activation represents a secondary reaction to a primary degenerative process occurring in the CNS. Conceptually, this causes myelin instability and disintegration that is followed, only in second instance, by a massive immunological activation to clear up the debris. Our aim is to collect the state-of-the-art of the current knowledge in the field. We would like to highlight which of the two hypotheses describes more accurately the mechanism involved in MS trigger.
The majority of the pathological observations can be equally described by both theories due to the heterogeneity of clinical manifestations and the technical difficulties in dissecting the triggering mechanisms.
Hence, a hot topic in the field is now to clarify which comes first: (auto)immunity or degeneration? Determining MS onset mechanisms might have a tremendous impact on disease prevention and management, thanks to the identification of new potential targets.
In this Research Topic, we aim to provide a translational contribution to the ongoing active discussion on the MS causes. Starting from the current knowledge supporting either autoimmune or neurodegenerative diseases towards an epidemiological and genetic focus that could also contribute to unravel MS etiopathogenesis.
The Topic is designed in a way that Opinion/(mini)Review articles are primarily constituting the core of the project. Original research and technical articles falling into the different subtopics of our issue are also warmly welcomed. To this aim, we will consider contributions coming from different disciplines (e.g. immunology, neuropathology, clinical neuroscience, neuroimaging, etc..) and focusing on one of the following:
1. Evidence of a primary CNS vs. immune system involvement as the main cause of MS etiopathogenesis;
2. Conventional (e.g. EAE) vs. unconventional/new (e.g. cuprizone, transgenic) animal models of MS;
3. Molecular pathways explaining MS etiopathogenesis as an outside-in or an inside-out mechanism;
4. Knowledge from other diseases affecting the CNS and mainly having a neurodegenerative (e.g., Alzheimer disease, Parkinson disease, etc.) and/or autoimmune (e.g. neuromyelitis optica spectrum disorders, anti-myelin oligodendrocyte glycoprotein syndrome, other inflammatory CNS disorders) etiopathogenesis to better understand the causes of MS;
5. The role of innate and adaptive immune system following an outside-in vs. inside-out approach: B-cells, T-cells, macrophages, and microglia;
6. Genetic and environmental factors in support or against the two different theories of MS etiopathogenesis;
7. How recent technical developments (e.g., laboratory, neuroimaging, etc.) could contribute to the identification of MS causes.
Topic Editor Paolo Preziosa received speaker honoraria from Biogen Idec, Novartis, Merck Serono and ExceMED. The rest of Topic Editors declare no competing interests with regards to the Research Topic.
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