Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results

Sarparanta, J.; Jonson, Per Harald; Kawan, Sabita; Udd, Bjarne

doi:10.3390/ijms21041409

Cited by 56 publications

(53 citation statements)

References 526 publications

(1,260 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Acquired chaperonopathies are due to non-genetic chaperone defects such as defective post-translational modifications or mis regulated gene expression (Macario, 2007;Lupo et al, 2016). A few examples of known chaperonopathies include dominant distal myopathy (Hsp40), hypomyelinating distrophy (Hsp60), Charcot-Marie-Tooth disease (Hsp27), and Bardet-Biedl syndrome (BBS proteins) (Lupo et al, 2016;Álvarez-Satta et al, 2017;Palmio et al, 2020;Sarparanta et al, 2020). The mtHsp60 gene has been localized to chromosome 2 in humans.…”

Section: Chaperonopathies and The Role Of Mthsp60 In Diseasementioning

confidence: 99%

Complex Destabilization in the Mitochondrial Chaperonin Hsp60 Leads to Disease

Rodrı́guez

Salzen

Holguin

et al. 2020

Front. Mol. Biosci.

View full text Add to dashboard Cite

Several neurological disorders have been linked to mutations in chaperonin genes and more specifically to the HSPD1 gene. In humans, HSPD1 encodes the mitochondrial Heat Shock Protein 60 (mtHsp60) chaperonin, which carries out essential protein folding reactions that help maintain mitochondrial and cellular homeostasis. It functions as a macromolecular complex that provides client proteins an environment that favors proper folding in an ATP-dependent manner. It has been established that mtHsp60 plays a crucial role in the proper folding of mitochondrial proteins involved in ATP producing pathways. Recently, various single-point mutations in the mtHsp60 encoding gene have been directly linked to neuropathies and paraplegias. Individuals who harbor mtHsp60 mutations that negatively impact its folding ability display phenotypes with highly compromised muscle and neuron cells. Carriers of these mutations usually develop neuropathies and paraplegias at different stages of their lives mainly characterized by leg stiffness and weakness as well as degeneration of spinal cord nerves. These phenotypes are likely due to hindered energy producing pathways involved in cellular respiration resulting in ATP deprived cells. Although the complete protein folding mechanism of mtHsp60 is not well understood, recent work suggests that several of these mutations act by destabilizing the oligomeric stability of mtHsp60. Here, we discuss recent studies that highlight key aspects of the mtHsp60 mechanism with a focus on some of the known disease-causing point mutations, D29G and V98I, and their effect on the protein folding reaction cycle.

show abstract

Section: Chaperonopathies and The Role Of Mthsp60 In Diseasementioning

confidence: 99%

Complex Destabilization in the Mitochondrial Chaperonin Hsp60 Leads to Disease

Rodrı́guez

Salzen

Holguin

et al. 2020

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…Of prone interest is the emerging evidence that mutations in several genes encoding for heat shock proteins are associated with the development of (neuro-)muscular disorders [ 25 ]. In particular, mutations in BAG3 (BAG family molecular chaperone regulator 3), CRYAB (α-crystallin B chain), and DNAJB6 (DnaJ homolog subfamily B member 6) are known to cause individual forms of muscular dystrophy [ 26 , 27 , 31 , 32 ].…”

Section: Endoplasmic Reticulum (Er)-stress and Unfolded Protein Rementioning

confidence: 99%

Cellular Stress in the Pathogenesis of Muscular Disorders—From Cause to Consequence

Mensch

Zierz

2020

IJMS

View full text Add to dashboard Cite

Cellular stress has been considered a relevant pathogenetic factor in a variety of human diseases. Due to its primary functions by means of contractility, metabolism, and protein synthesis, the muscle cell is faced with continuous changes of cellular homeostasis that require rapid and coordinated adaptive mechanisms. Hence, a prone susceptibility to cellular stress in muscle is immanent. However, studies focusing on the cellular stress response in muscular disorders are limited. While in recent years there have been emerging indications regarding a relevant role of cellular stress in the pathophysiology of several muscular disorders, the underlying mechanisms are to a great extent incompletely understood. This review aimed to summarize the available evidence regarding a deregulation of the cellular stress response in individual muscle diseases. Potential mechanisms, as well as involved pathways are critically discussed, and respective disease models are addressed. Furthermore, relevant therapeutic approaches that aim to abrogate defects of cellular stress response in muscular disorders are outlined.

show abstract

“…HSPB6 and CRYAB are two members of small heat shock protein famlily (sHSPs) that confer cells the ability to survive under stress conditions (32,33). Previous study discovered that mesenchymal stem cells overexpression HSPB6 rendered cell resistance to oxidative stress via increasing secretion of growth factors including VEGF, FGF-2, and IGF-1(34).…”

Section: Discussionmentioning

confidence: 99%

Detecting Hub Genes Associated With Lauren Subtype of Gastric Cancer by Weighted Gene Co-Expression Network Analysis

Xu¹,

Yao²,

Qu³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Gastric cancer is a rather heterogeneous type of malignant tumor. Among the several classification system, Lauren classification can reflect biological and pathological differences of different gastric cancer.Method to provide systematic biological perspectives, we employ weighted gene co-expression network analysis to reveal transcriptomic characteristics of gastric cancer. GSE15459 and TCGA STAD dataset were downloaded. Co-expressional network was constructed and gene modules were identified. Result Two key modules blue and red were suggested to be associated with diffuse gastric cancer. Functional enrichment analysis of genes from the two modules was performed. Validating in TCGA STAD dataset, we propose 10 genes TNS1, PGM5, CPXM2, LIMS2, AOC3, CRYAB, ANGPTL1, BOC and TOP2A to be hub-genes for diffuse gastric cancer. Finally these ten genes were associated with gastric cancer survival. Conclusion More attention need to be paid and further experimental study is required to elucidate the role of these genes.

show abstract

Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results

Cited by 56 publications

References 526 publications

Complex Destabilization in the Mitochondrial Chaperonin Hsp60 Leads to Disease

Complex Destabilization in the Mitochondrial Chaperonin Hsp60 Leads to Disease

Cellular Stress in the Pathogenesis of Muscular Disorders—From Cause to Consequence

Detecting Hub Genes Associated With Lauren Subtype of Gastric Cancer by Weighted Gene Co-Expression Network Analysis

Contact Info

Product

Resources

About