Results 91 to 100 of about 23,025 (248)

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

Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic. [PDF]

Cell, 2021
Logan T, Simon MJ, Rana A, Cherf GM, Srivastava A, Davis SS, Low RLY, Chiu CL, Fang M, Huang F, Bhalla A, Llapashtica C, Prorok R, Pizzo ME, Calvert MEK, Sun EW, Hsiao-Nakamoto J, Rajendra Y, Lexa KW, Srivastava DB, van Lengerich B, Wang J, Robles-Colmenares Y, Kim DJ, Duque J, Lenser M, Earr TK, Nguyen H, Chau R, Tsogtbaatar B, Ravi R, Skuja LL, Solanoy H, Rosen HJ, Boeve BF, Boxer AL, Heuer HW, Dennis MS, Kariolis MS, Monroe KM, Przybyla L, Sanchez PE, Meisner R, Diaz D, Henne KR, Watts RJ, Henry AG, Gunasekaran K, Astarita G, Suh JH, Lewcock JW, DeVos SL, Di Paolo G.   +52 more
europepmc   +1 more source

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

Deficiency in NPC2 results in disruption of mitochondria-late endosome/lysosomes contact sites and endo-lysosomal lipid dyshomeostasis

Scientific Reports
Dysfunction of the endo-lysosomal intracellular Cholesterol transporter 2 protein (NPC2) leads to the onset of Niemann–Pick Disease Type C (NPC), a lysosomal storage disorder.
Raffaele Pastore, Lihang Yao, Nathan Hatcher, Martin Helley, Janet Brownlees, Radha Desai   +5 more
doaj   +1 more source

A systematic review and integrative sequential explanatory narrative synthesis: The psychosocial impact of parenting a child with a lysosomal storage disorder. [PDF]

J Inherit Metab Dis, 2022
Hassall S, Smith DM, Rust S, Wittkowski A.   +3 more
europepmc   +1 more source

Quantitative Visualization of Intracellular Nanometabolism Using Peak‐Shifted Dual‐State Emissive FRET Nanoprobes

Advanced Science, EarlyView.
This study reveals the long‐elusive intracellular dissolution mechanism of carrier‐free nanomedicines. By utilizing peak‐shifted dual‐state emissive FRET nanoprobes (PDFNPs) that undergo a distinct ratiometric fluorescence peak shift upon disassembly, we achieve real‐time, quantitative tracking of dissolution kinetics in live cells.
Farsai Taemaitree, Jinwoo Sung, Yutaro Miki, Ryuju Suzuki, Yoshitaka Koseki, Kunikazu Ishii, Minsang Kim, Keita Tanita, Kota Sato, Toru Nakazawa, Satoshi Katsube, Daisuke Unabara, Tasuku Hamaguchi, Keisuke Kawakami, Koji Yonekura, Akihide Hibara, Atsushi Wakamiya, Hiroshi Uji‐I, Hitoshi Kasai   +18 more
wiley   +1 more source

Neuronal genetic rescue normalizes brain network dynamics in a lysosomal storage disorder despite persistent storage accumulation. [PDF]

Mol Ther, 2022
Ahrens-Nicklas RC, Tecedor L, Hall AF, Kane O, Chung RJ, Lysenko E, Marsh ED, Stein CS, Davidson BL.   +8 more
europepmc   +1 more source

Molecular Glue Degraders Enhance CAPRIN1‐Dependent Lysosomal Degradation of APP and Reduce Amyloid β in Alzheimer's Disease

Advanced Science, EarlyView.
A new class of lysosome‐directed molecular glue degraders selectively enhance CAPRIN1–APP interactions, driving APP degradation and reducing amyloid‐β production in human neurons and Alzheimer's disease mouse models. This CAPRIN1‐dependent targeted protein degradation strategy reveals a previously unrecognized therapeutic approach for disrupting the ...
Sunghan Jung, Xu Wang, Bin Liu, Raktim Roy, Nancy Jaiswal, Ratan K. Rai, Yuichiro Takagi, Cen Gao, Lifan Zeng, Ho‐Yin Lo, Reagan K. Wohlford, Ryan K. Higgins, Bruce T. Lamb, Anantha Shekhar, Anita C. Bellail, Chunhai Hao   +15 more
wiley   +1 more source

SIRT7‐Mediated H2BK120 Succinylation Drives Aberrant Mitophagy in Sepsis‐Associated Cognitive Dysfunction

Advanced Science, EarlyView.
Sepsis triggers hippocampal SIRT7 loss, promoting histone H2B succinylation and activation of the PD‐1/PD‐L1–PINK1 axis. This metabolic‐epigenetic cascade drives aberrant mitophagy and neuronal injury, ultimately causing cognitive deficits. Targeting SIRT7‐dependent succinylation offers a potential strategy to protect brain function during sepsis ...
Na Meng, Jiateng Zhou, Xiaoyu Guo, Ting Hong, Xuelian Li, Xingyu Wei, Chanhua Zhang, Xixue Zhang, Songbin Liu, Yulin Zhang, Liangfang Yao, Lina Huang, Weidong Gu   +12 more
wiley   +1 more source

Multifunctional Nanovaccine‐Radiotherapy Synergy Drives Anti‐Tumor Immunity via Multi‐Cascade Cell Death for Pancreatic Cancer Therapy

Advanced Science, EarlyView.
Machine‐learning‐driven transcriptomic analysis identifies FSTL3 as a key tumor‐microenvironment regulator in desmoplastic pancreatic adenocarcinoma. A cRGD‐modified liposome co‐loading gemcitabine and siFSTL3 serves as an irradiation‐triggered in situ nanovaccine. It synergizes with radiotherapy to induce ferroptosis and immunogenic cell death through
Chengyi Huang, Yushu Han, Xiang Liu, Chuanhao Wang, Xiaofei Zhu, Di Chen, Yangyang Gong, Liang Chen, Wenjuan Chen, Zhenyuan Miao, Bufu Tang, Huojun Zhang   +11 more
wiley   +1 more source