Innate immune activation in neurodegenerative diseases

Castro-Gomez, Sergio; Heneka, Michael T.

doi:10.1016/j.immuni.2024.03.010

Cited by 6 publications

(2 citation statements)

References 273 publications

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Section: Concluding Perspectives and Future Directions In Trem2 And S...mentioning

confidence: 99%

“…However, the interplay between protein aggregation and neuroinflammation presents conflicting data (Mosley, 2015;Labzin et al, 2018), with some studies suggesting that misfolded Aβ fibrils disrupt brain homeostasis, while others argue that protein accumulation triggers inflammation. The initiating factor of AD-be it protein deposition or disturbed homeostasis-remains uncertain, though the involvement of the innate immune system is clear (Castro-Gomez and Heneka, 2024). Elevated serum levels of sTREM2 may also serve as a promising biomarker for identifying mild cognitive impairment in patients with obstructive sleep apnea, correlating with lower cognitive performance as assessed by the Montreal Cognitive Assessment (Jiahuan et al, 2022).…”

Section: Overview Of Findingsmentioning

confidence: 99%

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Decoding sTREM2: its impact on Alzheimer’s disease – a comprehensive review of mechanisms and implications

Lin,

Kong,

Chen

et al. 2024

Front. Aging Neurosci.

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Soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2) plays a crucial role in the pathogenesis of Alzheimer’s disease (AD). This review comprehensively examines sTREM2’s involvement in AD, focusing on its regulatory functions in microglial responses, neuroinflammation, and interactions with key pathological processes. We discuss the dynamic changes in sTREM2 levels in cerebrospinal fluid and plasma throughout AD progression, highlighting its potential as a therapeutic target. Furthermore, we explore the impact of genetic variants on sTREM2 expression and its interplay with other AD risk genes. The evidence presented in this review suggests that modulating sTREM2 activity could influence AD trajectory, making it a promising avenue for future research and drug development. By providing a holistic understanding of sTREM2’s multifaceted role in AD, this review aims to guide future studies and inspire novel therapeutic strategies.

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Section: Concluding Perspectives and Future Directions In Trem2 And S...mentioning

confidence: 99%

Section: Overview Of Findingsmentioning

confidence: 99%

Decoding sTREM2: its impact on Alzheimer’s disease – a comprehensive review of mechanisms and implications

Lin,

Kong,

Chen

et al. 2024

Front. Aging Neurosci.

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Detrimental but Not Doomed—Glial Activation in Rapid Eye Movement Sleep Behavior Disorder

Liu,

Sossi

2024

Movement Disorders

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Axon length-dependent synapse loss is mediated by neuronal cytokine-induced glial phagocytosis

Tenedini,

Yin,

Huang

et al. 2024

Preprint

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Many neurodegenerative disorders (NDDs) preferentially affect neurons with long or complex axonal arbors, but our understanding of this specific vulnerability is limited. UsingDrosophilalarval class IV dendrite arborization (C4da) neurons, we found that neuronal activation of the integrated stress response (ISR) induces axon length-dependent degeneration (LDD). We identified the Interleukin-6 homologue unpaired 3 (upd3) as both necessary and sufficient for LDD in C4da neurons. Upd3 recruits glial cells to phagocytose presynapses preferentially on neurons with long axons, revealing an intrinsic axon length-dependent vulnerability to glia-mediated presynapse removal. Finally, we found that axon length-dependent presynapse loss in fly models of human NDDs utilized this pathway. Altogether, our studies identify inflammatory cytokine signaling from neurons to glia as a key determinant in axon length-dependent vulnerability.One-Sentence SummarySensory neurons exhibit intrinsic length-dependent vulnerability to presynapse removal driven by cytokine activation of glia.

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Innate immune activation in neurodegenerative diseases

Cited by 6 publications

References 273 publications

Decoding sTREM2: its impact on Alzheimer’s disease – a comprehensive review of mechanisms and implications

Decoding sTREM2: its impact on Alzheimer’s disease – a comprehensive review of mechanisms and implications

Detrimental but Not Doomed—Glial Activation in Rapid Eye Movement Sleep Behavior Disorder

Axon length-dependent synapse loss is mediated by neuronal cytokine-induced glial phagocytosis

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