Molecular and pharmacological chaperones for SOD1

Wright, Gareth S. A.

doi:10.1042/bst20200318

Cited by 13 publications

(10 citation statements)

References 89 publications

(134 reference statements)

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“…Importantly, CCS does not have the same ability to promote zinc binding to SOD1 mutants as it does for SOD1 wild type [ 248 ]. Other important SOD1 chaperones are the HSP family, for example, HSP70 which has a role in SOD1 folding, refolding, degradation, and together with co-chaperones, they reduce the exposure of aggregation-prone regions of SOD1, thus preventing aggregation [ 349 ]. The DNAJ (HSP40) assists HSP70 by regulating ATPase activity, aids in polypeptide binding, and prevention of premature polypeptide folding [ 350 ].…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

“…The HSPB8-BAG3-HSP70 complex allows cargo delivery to autophagy for degradation. Consequently, HSPB8 down-regulation results in increased accumulation of misfolded proteins and DPRs [ 351 ], and its overexpression was found to promote the clearance of mutant SOD1 [ 349 ]. Furthermore, overexpression of HSPB8 promotes the clearance of mutant SOD1, and double transgenic mice overexpressing HSP27 and mutant SOD1 exhibit increased survival of spinal MNs than mice overexpressing mutant SOD1 alone [ 349 ].…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

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All Roads Lead to Rome: Different Molecular Players Converge to Common Toxic Pathways in Neurodegeneration

Argueti-Ostrovsky

Alfahel

Kahn

et al. 2021

Cells

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Multiple neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD) are being suggested to have common cellular and molecular pathological mechanisms, characterized mainly by protein misfolding and aggregation. These large inclusions, most likely, represent an end stage of a molecular cascade; however, the soluble misfolded proteins, which take part in earlier steps of this cascade, are the more toxic players. These pathological proteins, which characterize each specific disease, lead to the selective vulnerability of different neurons, likely resulting from a combination of different intracellular mechanisms, including mitochondrial dysfunction, ER stress, proteasome inhibition, excitotoxicity, oxidative damage, defects in nucleocytoplasmic transport, defective axonal transport and neuroinflammation. Damage within these neurons is enhanced by damage from the nonneuronal cells, via inflammatory processes that accelerate the progression of these diseases. In this review, while acknowledging the hallmark proteins which characterize the most common NDDs; we place specific focus on the common overlapping mechanisms leading to disease pathology despite these different molecular players and discuss how this convergence may occur, with the ultimate hope that therapies effective in one disease may successfully translate to another.

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Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

All Roads Lead to Rome: Different Molecular Players Converge to Common Toxic Pathways in Neurodegeneration

Argueti-Ostrovsky

Alfahel

Kahn

et al. 2021

Cells

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“…Moreover, co-translational folding of GFP occurs more efficiently than after its chemical denaturation, which can be partially explained by the proposition that gradual polypeptide synthesis occurring in ribosomes facilitates the acquisition of more favorable conformations for correct folding [ 132 ]. Several soluble β-barrels, such as human SOD1, require special chaperones (hCCS in the case of SOD1) for correct folding and maturation, which occur through a series of consequent intermediate steps [ 133 ]. The misfolded aggregated state of SOD1 has also been shown to interact with molecular chaperones [ 134 , 135 ].…”

Section: Folding Of β-Barrel Proteins and Their Aggregationmentioning

confidence: 99%

β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis

Sulatskaya

Kosolapova

Bobylev

et al. 2021

IJMS

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Insoluble protein aggregates with fibrillar morphology called amyloids and β-barrel proteins both share a β-sheet-rich structure. Correctly folded β-barrel proteins can not only function in monomeric (dimeric) form, but also tend to interact with one another—followed, in several cases, by formation of higher order oligomers or even aggregates. In recent years, findings proving that β-barrel proteins can adopt cross-β amyloid folds have emerged. Different β-barrel proteins were shown to form amyloid fibrils in vitro. The formation of functional amyloids in vivo by β-barrel proteins for which the amyloid state is native was also discovered. In particular, several prokaryotic and eukaryotic proteins with β-barrel domains were demonstrated to form amyloids in vivo, where they participate in interspecies interactions and nutrient storage, respectively. According to recent observations, despite the variety of primary structures of amyloid-forming proteins, most of them can adopt a conformational state with the β-barrel topology. This state can be intermediate on the pathway of fibrillogenesis (“on-pathway state”), or can be formed as a result of an alternative assembly of partially unfolded monomers (“off-pathway state”). The β-barrel oligomers formed by amyloid proteins possess toxicity, and are likely to be involved in the development of amyloidoses, thus representing promising targets for potential therapy of these incurable diseases. Considering rapidly growing discoveries of the amyloid-forming β-barrels, we may suggest that their real number and diversity of functions are significantly higher than identified to date, and represent only “the tip of the iceberg”. Here, we summarize the data on the amyloid-forming β-barrel proteins, their physicochemical properties, and their biological functions, and discuss probable means and consequences of the amyloidogenesis of these proteins, along with structural relationships between these two widespread types of β-folds.

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“…Abnormal expression of many genes has been shown to play an important role in the occurrence and development of ALS. Superoxide dismutase 1 (SOD1) is a small protein that contributes to partial resistance to oxidative stress [ 16 ]. Approximately 15% of fALS cases are caused by SOD1 mutations [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Regulatory Factors and Prognostic Markers in Amyotrophic Lateral Sclerosis

Sun

et al. 2022

Antioxidants

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of motor neurons, leading to muscle atrophy, paralysis and even death. Immune disorder, redox imbalance, autophagy disorder, and iron homeostasis disorder have been shown to play critical roles in the pathogenesis of ALS. However, the exact pathogenic genes and the underlying mechanism of ALS remain unclear. The purpose of this study was to screen for pathogenic regulatory genes and prognostic markers in ALS using bioinformatics methods. We used Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), and expression regulation network analysis to investigate the function of differentially expressed genes in the nerve tissue, lymphoid tissue, and whole blood of patients with ALS. Our results showed that the up-regulated genes were mainly involved in immune regulation and inflammation, and the down-regulated genes were mainly involved in energy metabolism and redox processes. Eleven up-regulated transcription factors (CEBPB, CEBPD, STAT5A, STAT6, RUNX1, REL, SMAD3, GABPB2, FOXO1, PAX6, and FOXJ1) and one down-regulated transcription factor (NOG) in the nerve tissue of patients with ALS likely play important regulatory roles in the pathogenesis of ALS. Based on construction and evaluation of the ALS biomarker screening model, cluster analysis of the identified characteristic genes, univariate Cox proportional hazards regression analysis, and the random survival forest algorithm, we found that MAEA, TPST1, IFNGR2, and ALAS2 may be prognostic markers regarding the survival of ALS patients. High expression of MAEA, TPST1, and IFNGR2 and low expression of ALAS2 in ALS patients may be closely related to short survival of ALS patients. Taken together, our results indicate that immune disorders, inflammation, energy metabolism, and redox imbalance may be the important pathogenic factors of ALS. CEBPB, CEBPD, STAT5A, STAT6, RUNX1, REL, SMAD3, GABPB2, FOXO1, PAX6, FOXJ1, and NOG may be important regulatory factors linked to the pathogenesis of ALS. MAEA, TPST1, IFNGR2, and ALAS2 are potential important ALS prognostic markers. Our findings provide evidence on the pathogenesis of ALS, potential targets for the development of new drugs for ALS, and important markers for predicting ALS prognosis.

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Molecular and pharmacological chaperones for SOD1

Cited by 13 publications

References 89 publications

All Roads Lead to Rome: Different Molecular Players Converge to Common Toxic Pathways in Neurodegeneration

All Roads Lead to Rome: Different Molecular Players Converge to Common Toxic Pathways in Neurodegeneration

β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis

Identification of Regulatory Factors and Prognostic Markers in Amyotrophic Lateral Sclerosis

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