Search results for "PROTEOSTASIS"

GENETIC NEUROCHAPERONOPATHIES ASSOCIATED WITH CCT5 AND HSP60 VARIANTS: ANALYSIS OF THEIR MOLECULAR ANATOMY AND POSSIBLE PATHOGENIC IMPLICATIONS

2022

Homeostasis in the Central Dogma of molecular biology: the importance of mRNA instability

2019

Cell survival requires the control of biomolecule concentration, i.e. biomolecules should approach homeostasis. With information-carrying macromolecules, the particular concentration variation ranges depend on each type: DNA is not buffered, but mRNA and protein concentrations are homeostatically controlled, which leads to the ribostasis and proteostasis concepts. In recent years, we have studied the particular features of mRNA ribostasis and proteostasis in the model organism S. cerevisiae. Here we extend this study by comparing published data from three other model organisms: E. coli, S. pombe and cultured human cells. We describe how mRNA ribostasis is less strict than proteostasis. A co…

Oxidative stress, a new hallmark in the pathophysiology of Lafora progressive myoclonus epilepsy

2015

12 páginas, 4 figuras, 1 tabla

Nuclear involvement of the Cell Division Cycle 48 protein during the plant immune response

2023

The control of protein homeostasis, a balance between their synthesis and degradation, also called proteostasis, is essential for cell survival. Any imbalance of the proteome, for instance triggered by a stress, leads to an accumulation of misfolded proteins leading to proteotoxic stress that can induce cell death. The ubiquitin proteasome system (UPS) is a major actor in the selective degradation of misfolded proteins to preserve proteome balance.The chaperone-like Cdc48 is a member of the AAA+ ATPase enzyme family which isconserved in mammals (VCP), yeasts and plants (Cdc48: Cell Division Cycle 48/p97).Cdc48/VCP is a cytosolic and nuclear protein which segregates misfolded proteins fromsu…

Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo

2019

Dysfunction of autophagy and disturbed protein homeostasis are linked to the pathogenesis of human neurodegenerative diseases and the modulation of autophagy as the protein clearance process has become one key pharmacological target. Due to the role of sigma-1 receptors (Sig-1R) in learning and memory, and the described pleiotropic neuroprotective effects in various experimental paradigms, Sig-1R activation is recognized as one potential approach for prevention and therapy of neurodegeneration and, interestingly, in amyotrophic lateral sclerosis associated with mutated Sig-1R, autophagy is disturbed. Here we analyzed the effects of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hyd…

The deubiquitinase USP11 is a versatile and conserved regulator of autophagy

2021

Autophagy is a major cellular quality control system responsible for the degradation of proteins and organelles in response to stress and damage to maintain homeostasis. Ubiquitination of autophagy-related proteins or regulatory components is important for the precise control of autophagy pathways. Here, we show that the deubiquitinase ubiquitin-specific protease 11 (USP11) restricts autophagy and that KO of USP11 in mammalian cells results in elevated autophagic flux. We also demonstrate that depletion of the USP11 homolog H34C03.2 in Caenorhabditis elegans triggers hyperactivation of autophagy and protects the animals against human amyloid-β peptide 42 aggregation-induced paralysis. USP11…

Retinoic Acid and the Gut Microbiota in Alzheimer’s Disease: Fighting Back-to-Back?

2019

Background:There is growing evidence that the gut microbiota may play an important role in neurodegenerative diseases such as Alzheimer’s disease. However, how these commensals influence disease risk and progression still has to be deciphered.Objective:The objective of this review was to summarize current knowledge on the interplay between gut microbiota and retinoic acid. The latter one represents one of the important micronutrients, which have been correlated to Alzheimer’s disease and are used in initial therapeutic intervention studies.Methods:A selective overview of the literature is given with the focus on the function of retinoic acid in the healthy and diseased brain, its metabolism…

1,4 dihidropiridinski derivati povećavaju ekspresiju gena Psma3, Psmb5 i Psmc6 u glasničkoj RNA štakora

2021

The ubiquitin-proteasome system modifies different cellular and protein functions. Its dysregulation may lead to disrupted proteostasis associated with multiple pathologies and aging. Pharmacological regulation of proteasome functions is already an important part of the treatment of several diseases. 1,4-dihydropyridine (1,4-DHP) derivatives possess different pharmacological activities, including antiaging and neuroprotective. The aim of this study was to investigate the effects of several 1,4-DHP derivatives on mRNA expression levels of proteasomal genes Psma3, Psmb5, and Psmc6 in several organs of rats. Rats were treated with metcarbatone, etcarbatone, glutapyrone, styrylcarbatone, AV-153…