Skeletal muscle atrophy: From mechanisms to treatments

Pharmacological Research, Год журнала: 2021, Номер 172, С. 105807 - 105807

Опубликована: Авг. 10, 2021

Язык: Английский

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Deregulation of SPOP in Cancer

Cancer Research, Год журнала: 2022, Номер 83(4), С. 489 - 499

Опубликована: Дек. 13, 2022

Abstract Speckle-type POZ protein (SPOP) is a substrate-binding adaptor of the CULLIN3/RING-box1 E3 ubiquitin ligase complex. SPOP frequently mutated in prostate and endometrial cancers, whereas it overexpressed renal cell carcinoma (RCC). can mediate both degradable nondegradable polyubiquitination number substrates with diverse biological functions such as androgen receptor (AR), SRC-3, TRIM24, BRD4, PD-L1, 53BP1, GLP/G9a, c-Myc, SENP7, among others. Cancer-associated mutants often impair binding its to influence various cancer-relevant pathways, which include androgen/AR signaling, DNA repair methylation, cellular stress surveillance, cancer metabolism, immunity. Although recognized tumor suppressor acts like an oncoprotein RCC. This review provides overview recent progress understanding upstream regulators downstream targets, highlights significant impact mutations overexpression on pathogenesis, discusses potential targeting for treatment.

Язык: Английский

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Bap1/SMN axis in Dpp4+ skeletal muscle mesenchymal cells regulates the neuromuscular system

JCI Insight, Год журнала: 2022, Номер 7(10)

Опубликована: Май 22, 2022

The survival of motor neuron (SMN) protein is a major component the pre-mRNA splicing machinery and required for RNA metabolism. Although SMN has been considered fundamental gene central nervous system, due to its relationship with neuromuscular diseases, such as spinal muscular atrophy, recent studies have also revealed requirement in non-neuronal cells peripheral regions. Here, we report that fibro-adipogenic progenitor subpopulation expressing Dpp4 (Dpp4+ FAPs) system. Furthermore, reveal BRCA1-associated protein-1 (Bap1) crucial stabilization FAPs by preventing ubiquitination-dependent degradation. Inactivation Bap1 decreased levels accompanied degeneration junction, leading loss neurons muscle atrophy. Overexpression ubiquitination-resistant variant, SMNK186R, Bap1-null completely prevented degeneration. In addition, transplantation Dpp4+ FAPs, but not Dpp4– rescued defects. Our data role Bap1-mediated system provide possibility cell-based therapeutics treat diseases.

Язык: Английский

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HERC1 E3 Ubiquitin Ligase Is Necessary for Autophagy Processes and for the Maintenance and Homeostasis of Vesicles in Motor Nerve Terminals, but Not for Proteasomal Activity

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 793 - 793

Опубликована: Янв. 18, 2025

The ubiquitin proteasome system (UPS) is implicated in protein homeostasis. One of the proteins involved this HERC1 E3 ligase, which was associated with several processes including normal development and neurotransmission at neuromuscular junction (NMJ), autophagy projection neurons, myelination peripheral nervous system, among others. tambaleante (tbl) mouse model carries spontaneous mutation Gly483Glu substitution protein. Using model, we analyzed implication ligase activity UPS, autophagy, synaptic homeostasis brain muscle tissues. Regarding no differences were found its nor specific gene expression both tissues from tbl compared control littermates. Furthermore, use UPS inhibitor (MG-132), did not alter evoked neurotransmitter release levator auris longus (LAL) muscle. Interestingly, autophagy-related p62 significantly increased to Indeed, impaired observed Wortmannin. Finally, altered levels Clathrin Synaptophysin detected Altogether, our findings show that mice alters vesicular recycling without affecting proteasomal function.

Язык: Английский

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The HERC proteins and the nervous system

Seminars in Cell and Developmental Biology, Год журнала: 2021, Номер 132, С. 5 - 15

Опубликована: Ноя. 27, 2021

Язык: Английский

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Influence of DUX4 Expression in Facioscapulohumeral Muscular Dystrophy and Possible Treatments

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(11), С. 9503 - 9503

Опубликована: Май 30, 2023

Facioscapulohumeral muscular dystrophy (FSHD) represents the third most common form of and is characterized by muscle weakness atrophy. FSHD caused altered expression transcription factor double homeobox 4 (DUX4), which involved in several significantly pathways required for myogenesis regeneration. While DUX4 normally silenced majority somatic tissues healthy individuals, its epigenetic de-repression has been linked to FSHD, resulting aberrant cytotoxicity skeletal cells. Understanding how regulated functions could provide useful information not only further understand pathogenesis, but also develop therapeutic approaches this disorder. Therefore, review discusses role examining possible molecular mechanisms underlying disease as well novel pharmacological strategies targeting expression.

Язык: Английский

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Prenatal Skeletal Muscle Transcriptome Analysis Reveals Novel MicroRNA-mRNA Networks Associated with Intrauterine Growth Restriction in Pigs

Cells, Год журнала: 2021, Номер 10(5), С. 1007 - 1007

Опубликована: Апрель 24, 2021

Intrauterine growth restriction (IUGR) occurs in 15–20% of pig neonates and poses huge economic losses to the industry. IUGR piglets have reduced skeletal muscle growth, which may persist after birth. Prenatal is regulated by complex molecular pathways that are not well understood. MicroRNAs (miRNAs) emerged as main regulators vital biological processes body. This study was designed identify miRNA–mRNA networks regulating prenatal development pigs. We performed an integrative transcriptomic analysis longissimus dorsi from fetuses appropriate for gestational age (AGA) at 63 days post conception. Our data showed 47 miRNAs 3257 mRNAs were significantly upregulated, six 477 downregulated compared AGA fetuses. Moreover, upregulated negatively correlated can potentially target 326 genes, whereas 1291 genes. These enrichment critical fetal development, metabolism. The identified this serve indicators postnatal carcass quality.

Язык: Английский

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Upper motor neurons are a target for gene therapy and UCHL1 is necessary and sufficient to improve cellular integrity of diseased upper motor neurons

Gene Therapy, Год журнала: 2021, Номер 29(3-4), С. 178 - 192

Опубликована: Дек. 2, 2021

Язык: Английский

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Exocyst-mediated membrane trafficking of the lissencephaly-associated ECM receptor dystroglycan is required for proper brain compartmentalization

eLife, Год журнала: 2021, Номер 10

Опубликована: Фев. 23, 2021

To assemble a brain, differentiating neurons must make proper connections and establish specialized brain compartments. Abnormal levels of cell adhesion molecules disrupt these processes. Dystroglycan (Dg) is major non-integrin receptor, deregulation which associated with dramatic neuroanatomical defects such as lissencephaly type II or cobblestone brain. The previously established Drosophila model for was used to understand how Dg regulated in the During development, has spatiotemporally dynamic expression pattern, fine-tuning crucial accurate assembly. In addition, mass spectrometry analyses identified numerous components neurons, including several proteins exocyst complex. Data show that exocyst-based membrane trafficking allows its distinct essential morphogenesis. Further studies neuronal interactome will allow identification new factors involved development dystroglycanopathies advance disease diagnostics humans.

Язык: Английский

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Ubiquitylomics: An Emerging Approach for Profiling Protein Ubiquitylation in Skeletal Muscle

Journal of Cachexia Sarcopenia and Muscle, Год журнала: 2024, Номер unknown

Опубликована: Сен. 16, 2024

ABSTRACT Skeletal muscle is a highly adaptable tissue, finely tuned by various physiological and pathological factors. Whilst the pivotal role of skeletal in overall health widely acknowledged, unravelling underlying molecular mechanisms poses ongoing challenges. Protein ubiquitylation, crucial post‐translational modification, involved regulating most biological processes. This widespread impact achieved through diverse set enzymes capable generating structurally functionally distinct ubiquitin modifications on proteins. The complexity protein ubiquitylation has presented significant challenges not only identifying ubiquitylated proteins but also characterising their functional significance. Mass spectrometry enables in‐depth analysis modification status, offering powerful tool for studying its diversity: an approach termed ubiquitylomics. Ubiquitylomics been employed to tackle different perspectives including limited global quantification substrates linkages, site recognition crosstalk with other modifications. As field mass continues evolve, usage ubiquitylomics unravelled novel insights into regulatory governing biology. However, research predominantly conducted cellular models, limiting our understanding signalling events driving By integrating intricate landscape dynamic shifts physiology, promises deepen biology lay foundation developing transformative muscle‐related therapeutics. review aims articulate how can be utilised researchers address aspects muscle. We explore methods used experiments, highlight relevant literature employing context outline considerations experimental design.

Язык: Английский

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