Impaired unfolded protein response in the degeneration of cochlea cells in a mouse model of age-related hearing loss

2015 ◽  
Vol 70 ◽  
pp. 61-70 ◽  
Author(s):  
Wenwen Wang ◽  
Yu Sun ◽  
Sen Chen ◽  
Xingxing Zhou ◽  
Xia Wu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Mouse Model ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
Age Related ◽  
Protein Response ◽  
Age Related Hearing Loss

scholarly journals Two human metabolites rescue a C. elegans model of Alzheimer’s disease via a cytosolic unfolded protein response

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Priyanka Joshi ◽  
Michele Perni ◽  
Ryan Limbocker ◽  
Benedetta Mannini ◽  
Sam Casford ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Unfolded Protein Response ◽  
Neurodegenerative Disorders ◽  
C Elegans ◽  
Unfolded Protein ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
Protein Response

AbstractAge-related changes in cellular metabolism can affect brain homeostasis, creating conditions that are permissive to the onset and progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Although the roles of metabolites have been extensively studied with regard to cellular signaling pathways, their effects on protein aggregation remain relatively unexplored. By computationally analysing the Human Metabolome Database, we identified two endogenous metabolites, carnosine and kynurenic acid, that inhibit the aggregation of the amyloid beta peptide (Aβ) and rescue a C. elegans model of Alzheimer’s disease. We found that these metabolites act by triggering a cytosolic unfolded protein response through the transcription factor HSF-1 and downstream chaperones HSP40/J-proteins DNJ-12 and DNJ-19. These results help rationalise previous observations regarding the possible anti-ageing benefits of these metabolites by providing a mechanism for their action. Taken together, our findings provide a link between metabolite homeostasis and protein homeostasis, which could inspire preventative interventions against neurodegenerative disorders.

scholarly journals N-acetylcysteine Treatment Reduces Age-related Hearing Loss and Memory Impairment in the Senescence-Accelerated Prone 8 (SAMP8) Mouse Model

2018 ◽  
Vol 9 (4) ◽  
pp. 664 ◽  
Author(s):  
Aurore Marie ◽  
Johann Meunier ◽  
Emilie Brun ◽  
Susanna Malmstrom ◽  
Veronique Baudoux ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Mouse Model ◽  
Memory Impairment ◽  
Samp8 Mouse ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Altered Unfolded Protein Response Is Implicated in the Age-Related Exacerbation of Proteinuria-Induced Proximal Tubular Cell Damage

2013 ◽  
Vol 183 (3) ◽  
pp. 774-785 ◽  
Author(s):  
Naoko Takeda ◽  
Shinji Kume ◽  
Yuki Tanaka ◽  
Yoshikata Morita ◽  
Masami Chin-Kanasaki ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Cell Damage ◽  
Proximal Tubular Cell ◽  
Tubular Cell ◽  
Unfolded Protein ◽  
Age Related ◽  
Proximal Tubular ◽  
Protein Response

scholarly journals Deletion of Tmtc4 activates the unfolded protein response and causes postnatal hearing loss

2018 ◽  
Vol 128 (11) ◽  
pp. 5150-5162 ◽  
Author(s):  
Jiang Li ◽  
Omar Akil ◽  
Stephanie L. Rouse ◽  
Conor W. McLaughlin ◽  
Ian R. Matthews ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

SIRT1 expression in the cochlea and auditory cortex of a mouse model of age-related hearing loss

2014 ◽  
Vol 51 ◽  
pp. 8-14 ◽  
Author(s):  
Hao Xiong ◽  
Min Dai ◽  
Yongkang Ou ◽  
Jiaqi Pang ◽  
Haidi Yang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Mouse Model ◽  
Auditory Cortex ◽  
Sirt1 Expression ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Pathogenic tau does not drive activation of the unfolded protein response

2019 ◽  
Vol 294 (25) ◽  
pp. 9679-9688 ◽  
Author(s):  
Aleksandra P. Pitera ◽  
Ayodeji A. Asuni ◽  
Vincent O'Connor ◽  
Katrin Deinhardt
Keyword(s):  
Endoplasmic Reticulum ◽  
Mouse Model ◽  
Neurodegenerative Diseases ◽  
Unfolded Protein Response ◽  
Neuronal Cultures ◽  
Critical Determinant ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

The unfolded protein response (UPR) is commonly associated with a range of neurodegenerative diseases, and targeting UPR components has been suggested as a therapeutic strategy. The UPR surveys protein folding within the endoplasmic reticulum. However, many of the misfolded proteins that accumulate in neurodegeneration are localized so that they do not directly cause endoplasmic reticulum triggers that activate this pathway. Here, using a transgenic mouse model and primary cell cultures along with quantitative PCR, immunoblotting, and immunohistochemistry, we tested whether the UPR is induced in in vivo and in vitro murine models of tauopathy that are based on expression of mutant tauP301L. We found no evidence for the UPR in the rTg4510 mouse model, in which mutant tau is transgenically expressed under the control of tetracycline-controlled transactivator protein. This observation was supported by results from acute experiments in which neuronal cultures expressed mutant tau and accumulated misfolded cytoplasmic tau aggregates but exhibited no UPR activation. These results suggest that the UPR is not induced as a response to tau misfolding and aggregation despite clear evidence for progressive cellular dysfunction and degeneration. We propose that caution is needed when evaluating the implied significance of the UPR as a critical determinant across major neurodegenerative diseases.

Sign in / Sign up

Export Citation Format

Share Document