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- W2912466497 abstract "Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with clear similarities regarding their clinical, genetic and pathological features. Both are progressive, lethal disorders, with no current curative treatment available. Several genes that correlated with ALS and FTD are implicated in the same molecular pathways. Strikingly, many of these genes are not exclusively expressed in neurons, but also in glial cells, suggesting a multicellular pathogenesis. Moreover, chronic inflammation is a common feature observed in ALS and FTD, indicating an essential role of microglia, the resident immune cells of the central nervous system, in disease development and progression. In this review, we will provide a comprehensive overview of the implications of microglia in ALS and FTD. Specifically, we will focus on the role of impaired phagocytosis and increased inflammatory responses and their impact on microglial function. Several genes associated with the disorders can directly be linked to microglial activation, phagocytosis and neuroinflammation. Other genes associated with the disorders are implicated in biological pathways involved in protein degradation and autophagy. In general such mutations have been shown to cause abnormal protein accumulation and impaired autophagy. These impairments have previously been linked to affect the innate immune system in the central nervous system through inappropriate activation of microglia and neuroinflammation, highlighted in this review. Although it has been well established that microglia play essential roles in neurodegenerative disorders, the precise underlying mechanisms remain to be elucidated." @default.
- W2912466497 created "2019-02-21" @default.
- W2912466497 creator A5012307947 @default.
- W2912466497 creator A5090412968 @default.
- W2912466497 date "2019-04-01" @default.
- W2912466497 modified "2023-09-29" @default.
- W2912466497 title "Implications of Microglia in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia" @default.
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- W2912466497 doi "https://doi.org/10.1016/j.jmb.2019.02.004" @default.
- W2912466497 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30763568" @default.
- W2912466497 hasPublicationYear "2019" @default.
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