Related Experiment Video
Updated: Jun 27, 2026
06:58
Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
Published on: October 18, 2024
Innate immune crosstalk in ALS/FTD pathogenesis
Xiaoqiu Shu1, Xinyuan Yu1, Pinglong Xu1,2
1Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
Cell Insight
|June 26, 2026
Summary
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) involve innate immune pathways like cGAS-STING and NLRP3 inflammasomes. Understanding this immune network is key for new therapies targeting neuroinflammation.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases characterized by protein aggregation, impaired proteostasis, and neuroinflammation.
- Innate immune activation is increasingly recognized as a driver of ALS/FTD progression, not just a response to neuronal damage.
Purpose of the Study:
- To review how genetic lesions and protein aggregates in ALS/FTD engage innate immune pathways.
- To explore the crosstalk among these immune pathways and its implications for disease progression.
Main Methods:
- Literature review of studies on ALS/FTD genetics, proteinopathies, and innate immunity.
- Analysis of the roles of cGAS-STING, NLRP3 inflammasomes, and TREM2-DAP12 signaling in ALS/FTD pathogenesis.
Main Results:
- ALS/FTD-associated genetic factors and protein aggregates (TDP-43, SOD1, FUS, dipeptide repeats) activate cGAS-STING, NLRP3 inflammasomes, and TREM2-DAP12 pathways.
- Crosstalk between cGAS-STING and NLRP3 amplifies inflammation; NLRP3-mediated TREM2 shedding may hinder microglial functions.
Conclusions:
- The interconnected innate immune network in ALS/FTD contributes to disease progression.
- Targeting this immune network offers potential for subtype definition, biomarker discovery, and combinatorial therapeutic strategies to modulate neuroinflammation and preserve microglial function.
Keywords:
Amyotrophic lateral sclerosisFrontotemporal dementiaMicrogliaNLRP3 inflammasomeNeuroinflammationTREM2cGAS-STINGMore Related Videos
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