Secretomics Alterations and Astrocyte Dysfunction in Human iPSC of Leukoencephalopathy with Vanishing White Matter

Deng, Jiong; Zhang, Jie; Gao, Kai; Yan, Wei; Zhou, Ling; Jiang, Yuwu; Wang, Jingmin; Wu, Ye

doi:10.1007/s11064-022-03765-z

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…Moreover, neurons and astrocytes exhibit differences in the localization and composition of eIF2B complexes, and their ISR outcomes vary when subjected to chronic stress and ISR inhibition (Hanson et al, 2023). Inactivating mutations in eIF2B, which are associated with Vanishing White Matter Disease, affect astrocytes and oligodendrocytes prior to neuron dysfunction (Dietrich et al, 2005;Dooves et al, 2016;Wisse et al, 2018;Zhou et al, 2019;Deng et al, 2022). Along this line, ISR modulation can have dramatically different results in neuronal cell types: adjusting the ISR in excitatory and somatostatin-positive inhibitory neurons, but not parvalbumin-positive inhibitory neurons, results in altered longterm memory consolidation (Sharma et al, 2020;Shrestha et al, 2020).…”

Section: Cell-type-specific Isr Wiringmentioning

confidence: 99%

Signaling plasticity in the integrated stress response

Boone,

Zappa

2023

Front. Cell Dev. Biol.

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The Integrated Stress Response (ISR) is an essential homeostatic signaling network that controls the cell’s biosynthetic capacity. Four ISR sensor kinases detect multiple stressors and relay this information to downstream effectors by phosphorylating a common node: the alpha subunit of the eukaryotic initiation factor eIF2. As a result, general protein synthesis is repressed while select transcripts are preferentially translated, thus remodeling the proteome and transcriptome. Mounting evidence supports a view of the ISR as a dynamic signaling network with multiple modulators and feedback regulatory features that vary across cell and tissue types. Here, we discuss updated views on ISR sensor kinase mechanisms, how the subcellular localization of ISR components impacts signaling, and highlight ISR signaling differences across cells and tissues. Finally, we consider crosstalk between the ISR and other signaling pathways as a determinant of cell health.

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Section: Cell-type-specific Isr Wiringmentioning

confidence: 99%

Signaling plasticity in the integrated stress response

Boone,

Zappa

2023

Front. Cell Dev. Biol.

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Don't ignore the middle: Distinct mnemonic functions of intermediate hippocampus

Whitley,

Briggs,

Sharma

et al. 2024

Hippocampus

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The dorsal region of the hippocampus (dHC) mediates many of the mnemonic functions traditionally associated with the hippocampus proper, such as spatial and episodic memory, whereas ventral hippocampus (vHC) has been extensively implicated in emotional memory and motivational processes. By contrast, the functions of the intermediate hippocampus (iHC) are far less understood. In this study, we aimed to investigate the mnemonic functions of iHC by reversibly inactivating iHC prior to testing memory in behavioral tasks dependent on the integrity of dHC, iHC, or vHC, namely, rapid place water maze, inhibitory avoidance, spontaneous alternation, and temporal ordering of odors. Given our previous findings showing that dHC and vHC are involved in mnemonic control of ingestive behavior, we also assessed the effects of iHC inactivation on sucrose intake. The results showed that pharmacological inhibition of iHC impairs rapid place water maze memory, which has been previously shown to be dependent on iHC but not dHC or vHC. iHC inactivation does not impact memory dependent on dHC (spontaneous alternation), vHC (temporal odor memory), or either dHC or vHC (inhibitory avoidance), and only modestly affects sucrose intake. These findings provide support for the involvement of iHC in mnemonic functions that are distinct from dHC and vHC and highlight the need to further advance our understanding of the functions of this hippocampal region that has been relatively understudied.

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