期刊
ACTA NEUROPATHOLOGICA
卷 137, 期 5, 页码 715-730出版社
SPRINGER
DOI: 10.1007/s00401-018-1933-9
关键词
Amyotrophic lateral sclerosis; Frontotemporal dementia; Neurodegeneration; Neuroinflammation
资金
- NIH [NS097545, NS069669]
- Muscular Dystrophy Association [352536]
- Cedars-Sinai ALS Research Fund
- Robert and Louise Schwab family
- [T32 GM118288]
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that overlap in their clinical presentation, pathology and genetics, and likely represent a spectrum of one underlying disease. In ALS/FTD patients, neuroinflammation characterized by innate immune responses of tissue-resident glial cells is uniformly present on end-stage pathology, and human imaging studies and rodent models support that neuroinflammation begins early in disease pathogenesis. Additionally, changes in circulating immune cell populations and cytokines are found in ALS/FTD patients, and there is evidence for an autoinflammatory state. However, despite the prominent role of neuro- and systemic inflammation in ALS/FTD, and experimental evidence in rodents that altering microglial function can mitigate pathology, therapeutic approaches to decrease inflammation have thus far failed to alter disease course in humans. Here, we review the characteristics of inflammation in ALS/FTD in both the nervous and peripheral immune systems. We further discuss evidence for direct influence on immune cell function by mutations in ALS/FTD genes including C9orf72, TBK1 and OPTN, and how this could lead to the altered innate immune system tone observed in these patients.
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