Results 121 to 130 of about 48,911 (292)

Phase Separation, Material State, and Condensate Fate in Mammalian Autophagy

Advanced Science, EarlyView.
ABSTRACT Biomolecular phase separation has emerged as a key organizing principle in macroautophagy (hereafter autophagy). In mammalian cells, phase‐separated condensates not only serve as substrates for selective degradation, but also act as dynamic platforms for cargo recognition, signaling integration, and autophagosome assembly.
Yuanqiang Lin, Mingran Dai, Enyong Dai, Rui Kang, Daniel J. Klionsky, Daolin Tang, Yu Sun, Ningning Lv, Junnan Jiang   +8 more
wiley   +1 more source

Walking the tightrope: proteostasis and neurodegenerative disease

, 2016
A characteristic of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), is the aggregation of specific proteins into protein inclusions and/or ...
Philip M Beart (20245164), Darren Saunders (20117955), Danny M Danny (20234412), Heath Ecroyd (19583602), Justin Yerbury (20136507), Neil R Cashman (10645424), Lezanne Ooi (19588228), Mark Wilson (19585432), Andrew G Dillin (20245161)   +8 more
core   +3 more sources

Impaired Chaperone‐Mediated Autophagy Accelerates Intervertebral Disc Degeneration by Inducing MIDN Accumulation to Target TSC2 for Proteasomal Degradation

Advanced Science, EarlyView.
This graphical abstract illustrates how chaperone‐mediated autophagy (CMA) regulates intervertebral disc degeneration (IDD). Under normal homeostasis (B), CMA degrades cytoplasmic Midnolin (MIDN) to maintain proteostasis. Under inflammatory stress (A), impaired CMA leads to cytoplasmic MIDN accumulation.
Xianglong Chen, Haiyang Gao, Wang Wu, Pengzhi Shi, Yuhang Chen, Anran Zhang, Zhangrong Cheng, Wenbo Wu, Zimu Yu, Yukun Zhang   +9 more
wiley   +1 more source

Metal Oxides Catalyze Formation of Dehydroamino Acids by Phosphate β‐Elimination Under Physiological Conditions

Angewandte Chemie, EarlyView.
Dehydroamino acids (DHAA) are atypical electrophilic sites that lead to crosslinked proteins in Alzheimer's disease (AD) brains. No catalyst for their formation has been known in humans. We report that metal oxides catalyze β‐elimination of phosphoserine and phosphothreonine in model peptides at pH 7.5°C and 37°C, yielding DHAAs.
Samuel W. Markovich, Brian L. Frey, Mark Scalf, Lloyd M. Smith   +3 more
wiley   +2 more sources

OAF Blocks SIAH1‐Mediated Degradation of SCPX, a Therapeutic Strategy for MASLD

Advanced Science, EarlyView.
This study shows OAF directly binds to SCPX and inhibits its interaction with the E3 ligase SIAH1, thereby protecting SCPX from ubiquitin‐dependent degradation and stabilizing its levels. This OAF‐SCPX axis represents a novel pathway in lipid homeostasis, highlighting OAF as a promising therapeutic candidate for MASLD.
Zongxi Li, Jingyue Song, Kaili Ma, Shunan Tang, Shuqian Wang, Wenya Ji, Chen Lu, Ting Zhang, Huaping Zheng, Xiaowei Zheng, Shanshan Lai, Cheng Deng   +11 more
wiley   +1 more source

Das Proteostasis System in Nematoden und Bäckerhefe

, 2016
In this work the chaperone related muscular proteostasis and the failure of cellular proteostasis were addressed. The balanced action of Hsc70 and its cofactors UNC-23 and DNJ-13 was found being crucial for the contribution of Hsc70 to muscle ...
Papsdorf, Katharina
core  

Near‐Infrared Fluorescent PROTAC Enables Theranostic Imaging and Selective Tau Degradation in Alzheimer's Disease

Advanced Science, EarlyView.
Here, we report a novel NIR fluorescent PROTAC platform that enables real‐time imaging and targeted degradation of Alzheimer's p‐Tau. Our lead compound effectively clears p‐Tau, reduces APP/Aβ, and alleviates cognitive deficits in AD mice. This work demonstrates a theranostic strategy for visualizing degradation and developing next‐generation AD ...
Ziwei Ren, Qian Yue, Ning Gao, Qiu‐Lian Hao, Yan Huo, Chuchu Li, Xinyue Leng, Lu‐Lu Sun, Maggie Pui Man Hoi, Hai‐Hao Han, Mingliang Ma, Xu‐Wen Li   +11 more
wiley   +1 more source

Phenylhydrazone-based endoplasmic reticulum proteostasis regulator compounds with enhanced biological activity

eLife
Pharmacological enhancement of endoplasmic reticulum (ER) proteostasis is an attractive strategy to mitigate pathology linked to etiologically diverse protein misfolding diseases.
Gabriel M Kline, Lisa Boinon, Adrian Guerrero, Sergei Kutseikin, Gabrielle Cruz, Marnie P Williams, Ryan J Paxman, William E Balch, Jeffery W Kelly, Tingwei Mu, R Luke Wiseman   +10 more
doaj   +1 more source

Targeted Lysosomal Degradation of Extracellular and Membrane Proteins: From Receptor Hijacking to Programmable Endolysosomal Routing

Advanced Science, EarlyView.
Targeted chimeric degraders engage extracellular or membrane proteins and endocytosable cell‐surface receptors, forming ternary complexes that induce receptor‐mediated internalization. Following endocytosis, post‐endocytic sorting—not internalization alone—determines target fate.
Ke Liu, Xiyan Wang, Xiaozhen Liu, Chaoqi He, Da Qian, Xuli Meng, Liquan Zhu   +6 more
wiley   +1 more source

Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis.

PLoS Genetics
Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in ...
Jeson J Li, Nan Xin, Chunxia Yang, Bo G Kim, Larissa A Tavizon, Ruth Hong, Jina Park, Travis I Moore, Rebecca George Tharyan, Adam Antebi, Hyun-Eui Kim   +10 more
doaj   +1 more source