Heat shock protein signaling in brain ischemia and injury

Kim, Jong Youl; Kim, Ji Won; Yenari, Midori A.

doi:10.1016/j.neulet.2019.134642

Cited by 49 publications

(36 citation statements)

References 102 publications

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“…Fig. 5A, red), which is consistent with the highly upregulated heat shock proteins in brain injury (Kim et al, 2020). Our analysis also highlighted that downregulated ECspecific DEGs were significantly enriched in pathways important for extracellular matrix (ECM) organization and modulating neural projection (Sup.…”

Section: Ec and Pc Specific Pathways Alteration Following Mtbisupporting

confidence: 82%

Secondary single-cell transcriptomic analysis reveals common molecular signatures of cerebrovascular injury between traumatic brain injury and aging

Guo

Zhang

Gómez‐Pinilla

et al. 2020

Preprint

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AbstractCerebrovascular injury is a common pathological feature of a spectrum of neurological disorders including traumatic brain injury (TBI), stroke, Alzheimer’s disease (AD), as well as aging. Vascular manifestations among these conditions are similar indeed, including the breakdown of the blood-brain barrier (BBB). However, whether there is a common molecular mechanism underlying the vascular changes among these conditions remains elusive. Here, we report secondary transcriptomic analysis on cerebrovascular cells based single-cell RNA-seq datasets of mouse models of mild TBI and aging, with a focus on endothelial cells and pericytes. We identify several molecular signatures commonly found between mTBI and aging vasculature, including Adamts1, Rpl23a, Tmem252, Car4, Serpine2, and Ndnf in endothelial cells, and Rps29 and Sepp1 in pericytes. These markers may represent the shared endophenotype of microvascular injury and be considered as cerebrovascular injury responsive genes. Additionally, pathway analysis on differentially expressed genes demonstrated alterations in common pathways between mTBI and aging, including vascular development and extracellular matrix pathways in endothelial cells. Hence, our analysis suggests that cerebrovascular injury triggered by different neurological conditions may share common molecular signatures, which may only be detected at the single-cell transcriptome level.

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Section: Ec and Pc Specific Pathways Alteration Following Mtbisupporting

confidence: 82%

Secondary single-cell transcriptomic analysis reveals common molecular signatures of cerebrovascular injury between traumatic brain injury and aging

Guo

Zhang

Gómez‐Pinilla

et al. 2020

Preprint

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show abstract

“…In addition, Hspb1 was upregulated in both iTRAQ and PRM, which has been associated with multiple sclerosis in the spinal cord [ 56 ]. Many proteins in the heat shock protein family have been found to be protective in neurodegenerative diseases and brain trauma [ 57 , 58 ]; thus, further research is required to explore the effects of other proteins in this family on post-traumatic protection. Inconsistency between PRM and iTRAQ also exists.…”

Section: Discussionmentioning

confidence: 99%

iTRAQ-based proteomic profiling reveals protein alterations after traumatic brain injury and supports thyroxine as a potential treatment

Zhang

Wang

et al. 2021

Mol Brain

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Traumatic brain injury (TBI) is a primary cause of disability and death across the world. Previously, RNA analysis was widely used to study the pathophysiological mechanisms underlying TBI; however, the relatively low correlation between the transcriptome and proteome revealed that RNA transcription abundance does not reliably predict protein abundance, which led to the emergence of proteomic research. In this study, an iTRAQ proteomics approach was applied to detect protein alterations after TBI on a large scale. A total of 3937 proteins were identified, and 146 proteins were significantly changed after TBI. Moreover, 23 upregulated proteins were verified by parallel reaction monitoring (PRM), and fold changes in 16 proteins were consistent with iTRAQ outcomes. Transthyretin (Ttr) upregulation has been demonstrated at the transcriptional level, and this study further confirmed this at the protein level. After treatment with thyroxine (T4), which is transported by Ttr, the effects of T4 on neuronal histopathology and behavioral performance were determined in vivo (TBI + T4 group). Brain edema was alleviated, and the integrity of the blood brain barrier (BBB) improved. Escape latency in the Morris water maze (MWM) declined significantly compared with the group without T4 treatment. Modified neurological severity scores (mNSS) of the TBI + T4 group decreased from day 1 to day 7 post-TBI compared with the TBI + saline group. These results indicate that T4 treatment has potential to alleviate pathologic and behavioral abnormalities post-TBI. Protein alterations after T4 treatment were also detected by iTRAQ proteomics. Upregulation of proteins like Lgals3, Gfap and Apoe after TBI were reversed by T4 treatment. GO enrichment showed T4 mainly affected intermediate filament organization, cholesterol transportation and axonal regeneration. In summary, iTRAQ proteomics provides information about the impact of TBI on protein alterations and yields insight into underlying mechanisms and pathways involved in TBI and T4 treatment. Finally, Ttr and other proteins identified by iTRAQ may become potential novel treatment targets post-TBI.

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“…HSPs protect synaptic function in the nervous system from environmental insults or pathological factors [18][19][20] (reviewed in [21]), and are also associated to neurodegenerative diseases, aberrant protein-induced neurotoxicity and disease progression [13]. The sHSPs family is involved as a non-canonical role in Drosophila development and other biological processes such as synaptic transmission [22].…”

Section: Introductionmentioning

confidence: 99%

Small heat shock proteins determine synapse number and neuronal activity during development

2020

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Environmental changes cause stress, Reactive Oxygen Species and unfolded protein accumulation which hamper synaptic activity and trigger cell death. Heat shock proteins (HSPs) assist protein refolding to maintain proteostasis and cellular integrity. Mechanisms regulating the activity of HSPs include transcription factors and posttranslational modifications that ensure a rapid response. HSPs preserve synaptic function in the nervous system upon environmental insults or pathological factors and contribute to the coupling between environmental cues and neuron control of development. We have performed a biased screening in Drosophila melanogaster searching for synaptogenic modulators among HSPs during development. We explore the role of two small-HSPs (sHSPs), sHSP23 and sHSP26 in synaptogenesis and neuronal activity. Both sHSPs immunoprecipitate together and the equilibrium between both chaperones is required for neuronal development and activity. The molecular mechanism controlling HSP23 and HSP26 accumulation in neurons relies on a novel gene (CG1561), which we name Pinkman (pkm). We propose that sHSPs and Pkm are targets to modulate the impact of stress in neurons and to prevent synapse loss.

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Heat shock protein signaling in brain ischemia and injury

Cited by 49 publications

References 102 publications

Secondary single-cell transcriptomic analysis reveals common molecular signatures of cerebrovascular injury between traumatic brain injury and aging

Secondary single-cell transcriptomic analysis reveals common molecular signatures of cerebrovascular injury between traumatic brain injury and aging

iTRAQ-based proteomic profiling reveals protein alterations after traumatic brain injury and supports thyroxine as a potential treatment

Small heat shock proteins determine synapse number and neuronal activity during development

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