Molecular Chaperones in Neurodegenerative Diseases: A Short Review

Bobori, Catherine; Theocharopoulou, Georgia; Vlamos, Panayiotis

doi:10.1007/978-3-319-57379-3_20

Cited by 17 publications

(21 citation statements)

References 59 publications

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“…Our results show that a dysfunction of the proteostasis system is implicated in the etiology of a series of highly prevalent psychiatric and neurodegenerative processes such as PD, dementia, and schizophrenia, among others [ 12 ]. Indeed, proteostasis alterations in the prefrontal cortex implicate proteome instability and accumulation of misfolded proteins [ 45 , 47 , 49 , 76 ] that could lead to detrimental behavioral and emotional functions in neuropsychiatric disorders [ 108 ].…”

Section: Discussionmentioning

confidence: 99%

“…Preserving proteostasis, that is, stable conditions during processes such as biogenesis, folding, trafficking, or degradation of proteins, is crucial to guaranteeing cell functions and the ability to elaborate pertinent reactions to tissue-specific chronic and acute stressors [ 11 ]. Dysregulation of the conservative mechanisms of proteostasis involves processes that are fundamental for the viability of postmitotic cells such as neurons and has been associated with several neurodegenerative diseases, such as AD, PD, and HD, among others [ 12 ]. Thereby, with increasing knowledge about changes in the tissue protein distribution, new pathogenic mechanisms could be revealed as potential therapeutic targets, especially in the study of the ubiquitin-proteasome system and molecular chaperones [ 8 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Proteostasis and Mitochondrial Role on Psychiatric and Neurodegenerative Disorders: Current Perspectives

et al. 2018

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Proteostasis involves processes that are fundamental for neural viability. Thus, protein misfolding and the formation of toxic aggregates at neural level, secondary to dysregulation of the conservative mechanisms of proteostasis, are associated with several neuropsychiatric conditions. It has been observed that impaired mitochondrial function due to a dysregulated proteostasis control system, that is, ubiquitin-proteasome system and chaperones, could also have effects on neurodegenerative disorders. We aimed to critically analyze the available findings regarding the neurobiological implications of proteostasis on the development of neurodegenerative and psychiatric diseases, considering the mitochondrial role. Proteostasis alterations in the prefrontal cortex implicate proteome instability and accumulation of misfolded proteins. Altered mitochondrial dynamics, especially in proteostasis processes, could impede the normal compensatory mechanisms against cell damage. Thereby, altered mitochondrial functions on regulatory modulation of dendritic development, neuroinflammation, and respiratory function may underlie the development of some psychiatric conditions, such as schizophrenia, being influenced by a genetic background. It is expected that with the increasing evidence about proteostasis in neuropsychiatric disorders, new therapeutic alternatives will emerge.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proteostasis and Mitochondrial Role on Psychiatric and Neurodegenerative Disorders: Current Perspectives

et al. 2018

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“…Recent work has shown that they are involved in the negative regulation to form aberrant, solid-like stress granules (Mateju et al, 2017). Molecular chaperone disorders usually induce toxic misfolded protein aggregates, which are more common in neurodegenerative diseases (Bobori, Theocharopoulou, & Vlamos, 2017;Qamar et al, 2018), but their link to cancer-related phase separation is only beginning to be understood.…”

Section: Interfering With Phase Separation-associated Client Moleculesmentioning

confidence: 99%

Protein phase separation: A novel therapy for cancer?

Wang

Chen

et al. 2020

British J Pharmacology

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In recent years, phase separation has been increasingly reported to play a pivotal role in a wide range of biological processes. Due to the close relationships between cancer and disorders in intracellular physiological function, the identification of new mechanisms involved in intracellular regulation has been regarded as a new direction for cancer therapy. Introducing the concept of phase separation into complex descriptions of disease mechanisms may provide many different insights. Here, we review the recent findings on the phase separation of cancer‐related proteins, describing the possible relationships between phase separation and key proteins associated with cancer and indicate possible regulatory modalities, especially drug candidates for phase separation, which may provide more effective strategies for cancer therapy.

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“…Via interactions with co-chaperones that regulate their localization and function, members of the Hsp70 (also known as Hspa) family of chaperones use the energy derived from ATP hydrolysis to maintain proper folding and/or turnover of synaptic proteins, and thereby, synaptic integrity (reviewed by Gorenberg and Chandra (2017)). As such, dysfunction of Hsp70 and other chaperone protein families has been implicated in several neurodegenerative diseases (for reviews see Kampinga and Bergink (2016), Ebrahimi-Fakhari et al (2011), Bobori et al (2017; Roodveldt et al (2017) and Lackie et al (2017)). Members of the Hsp70 family identified in the PANTHER pathway Parkinson disease were also identified in our cross-analysis with susceptibility genes associated with schizophrenia and ASD ( Fig.…”

Section: Panx1 Interacting Proteins In Neurodegenerative Diseases: a mentioning

confidence: 99%

Overlap in synaptic neurological condition susceptibility pathways and the neural pannexin 1 interactome revealed by bioinformatics analyses

Frederiksen

Wicki-Stordeur

Swayne

2019

Preprint

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The Pannexin 1 (Panx1) channel-forming protein is enriched in the central nervous system, and has been associated with several critical neurodevelopmental and plasticity functions; these include dendritic spine formation, neuronal network development, synaptic plasticity, and pathological brain states such as ischemia, epilepsy, and neurodegeneration. Despite major advances in understanding the properties and activation modes of Panx1, the Panx1 interactome remains largely uncharacterized. Considering that Panx1 has been implicated in critical neurodevelopmental and neurodegenerative processes and diseases, we investigated the Panx1 interactome (482 Panx1interacting proteins) identified from mouse N2a cells. These proteins were cross-analyzed with the postsynaptic proteome of the adult mouse brain previously identified by mass spectrometry (LC-MS/MS), and neurodegenerative disease and neurodevelopmental disorder susceptibility genes previously identified by genome-wide association studies (GWAS); and then further investigated using various bioinformatics tools (PAN-THER, GO, KEGG and STRING databases). A total of 104 of the Panx1-interacting proteins were located at the postsynapse, and 99 of these formed a 16-cluster protein-protein interaction (PPI) network (hub proteins: Eef2, Rab6A, Ddx39b, Mapk1, Fh1, Ndufv1 et cetera). The cross-analysis led to the discovery of proteins and candidate genes involved in synaptic function and homeostasis. Of particular note, our analyses also revealed that certain Panx1-interacting proteins are implicated in Parkinson disease, Alzheimer disease, Huntington disease, amyotrophic lateral sclerosis, schizophrenia, autism spectrum disorder and epilepsy. Altogether, our work revealed important clues to the role of Panx1 in neuronal function in health and disease by expanding our knowledge of the PPI network of Panx1, and unveiling previously unidentified Panx1-interacting proteins and networks involved in biological processes and disease. Panx1 | PPIs | pathway analysis | neurodegenerative diseases | neurodevelopmental disorders | Parkinson disease | Alzheimer disease | chaperones | vesicle-mediated transportFunctional annotation, categorization and overrepresentation analyses of the Panx1 interactome using the PANTHER database. Bioinformatics analysis of all proteins in our Panx1-interacting protein list (using UniProt accession numbers) was carried out using the PANTHER database v14.1 (Mi et al., 2013;Thomas et al., 2003), which is a curated database that includes several bioinformatics tools. The proteins (or their corresponding genes, depending on the nature of the analysis) were annotated to (i) PAN-THER protein classes from the PANTHER protein class ontology, (ii) gene ontology (GO) terms within the biological process, molecular function and cellular component domains from the GO knowledge base and (iii) PANTHER pathways created using the CellDesigner tool, a modelling tool for biochemical networks (Funahashi et al., 2008;Mi et al., 2019a;Mi et al., 2013). Note that PANTHER pa...

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Molecular Chaperones in Neurodegenerative Diseases: A Short Review

Cited by 17 publications

References 59 publications

Proteostasis and Mitochondrial Role on Psychiatric and Neurodegenerative Disorders: Current Perspectives

Proteostasis and Mitochondrial Role on Psychiatric and Neurodegenerative Disorders: Current Perspectives

Protein phase separation: A novel therapy for cancer?

Overlap in synaptic neurological condition susceptibility pathways and the neural pannexin 1 interactome revealed by bioinformatics analyses

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