Results 1 to 10 of about 21,037 (206)

Polyglutamine expansion induced dynamic misfolding of androgen receptor. [PDF]

Protein Sci
Abstract Spinal bulbar muscular atrophy (SBMA) is caused by a polyglutamine expansion (pQe) in the N‐terminal transactivation domain of the human androgen receptor (AR‐NTD), resulting in a combination of toxic gain‐ and loss‐of‐function mechanisms. The structural basis of these processes has not been resolved due to the disordered nature of the NTD ...
Heling LWHJ, Sheikhhassani V, Ng J, van Vliet M, Jiménez-Panizo A, Alegre-Martí A, Woodard J, van Roon-Mom W, McEwan IJ, Estébanez-Perpiñá E, Mashaghi A.   +10 more
europepmc   +2 more sources

Increased Activity-Dependent Bulk Endocytosis in Huntington's Disease Results From Huntingtin Haploinsufficiency. [PDF]

J Neurochem
Huntington's Disease (HD) is a neurodegenerative disorder characterised by an expanded CAG repeat mutation in the HTT gene, causing an extended polyglutamine tract in the huntingtin (htt) protein. We reveal that different neuronal subtypes derived from mice that model HD (Q140) display enhanced recruitment of activity‐dependent bulk endocytosis, the ...
Tan HCG, McAdam RL, Morton A, Cousin MA, Smillie KJ.   +4 more
europepmc   +2 more sources

Rewiring Neuroimmunity: Nanoplatform Innovations for CNS Disease Therapy

Advanced Therapeutics, EarlyView.
This review explores emerging nanoplatform strategies designed to modulate neuroimmune responses for treating central nervous system (CNS) disorders. It examines structural and microenvironmental barriers, advances in multifunctional and targeted nanotechnologies, and highlights clinical progress and translational challenges, offering insights into the
Muhammad Usman Akbar, Weiwei Guo, Xin Shen, Yimeng Fang, Yilin Liu, Peng‐Yuan Wang, Roey Elnathan, Yaping Chen   +7 more
wiley   +1 more source

Transient Interdomain Interactions Modulate the Monomeric Structural Ensemble and Self‐Assembly of Huntingtin Exon 1

Advanced Science, EarlyView.
Polyglutamine (polyQ) tract expansion (≥ 36 amino acids) within the N‐terminal region of the Huntingtin protein (Httex1) causes Huntington's disease (HD), for which the underlying causes are not well‐understood. The authors performed computer simulations to understand the cause of HD at the molecular level.
Priyesh Mohanty, Tien Minh Phan, Jeetain Mittal   +2 more
wiley   +1 more source

Establishment of a humanized SCA2 mouse model carrying a CAA disruption preventing CAG repeat expansion in pathogenic genes

Animal Models and Experimental Medicine, EarlyView.
In this study, we established a mouse model in which CAG repeats do not undergo microsatellite instability (MSI) across generations. A humanized ATXN2 cDNA with four CAA interruptions within 73 CAG expansions was inserted into the Rosa26 locus of C57BL/6J mice. At the same time, a 23 CAG control mouse model was also generated.
Yao Zhang, Yufei Li, Lin Zhang, Zhaoqing Li, Keqin Lin, Kai Huang, Zhaoqing Yang, Shaohui Ma, Hao Sun, Xiaochao Zhang   +9 more
wiley   +1 more source

Capture of Longitudinal Change in Real‐Life Walking in Cerebellar Ataxia Increases Patient Relevance and Effect Size

Movement Disorders, EarlyView.
ABSTRACT Background With disease‐modifying drugs for degenerative ataxias on the horizon, ecologically valid measures of gait performance that can detect patient‐relevant changes in trial‐like time frames are highly warranted. Objectives In this 2‐year longitudinal study, we aimed to unravel ataxic gait measures sensitive to longitudinal changes in ...
Jens Seemann, Theresa Beyme, Natalie John, Florian Harmuth, Martin Giese, Ludger Schöls, Dagmar Timmann, Matthis Synofzik, Winfried Ilg   +8 more
wiley   +1 more source

SQSTM1/p62 Orchestrates Skin Aging via USP7 Degradation

Aging Cell, EarlyView.
p62 exhibits diminished expression in aging skin and senescent cells. p62 serves to inhibit the accumulation of USP7 during senescence induction. The Tyr‐67 residue within the PB1 domain or Gln‐418 within the UBA domain of p62 forms a hydrogen bond with Ala‐993 of the Ubl5 domain of USP7.
Liu Chen, Xiaoping Wang, Yuchen Wang, Qingxin Yao, Yunyao Liu, Yongcheng Zhu, He Huang, Hedan Yang, Yin Yang, Yuan He, Lei Qiang   +10 more
wiley   +1 more source

Blood DDIT4 and TRIM13 Transcript Levels Mark the Early Stages of Machado–Joseph Disease

Annals of Neurology, Volume 98, Issue 1, Page 107-119, July 2025.
Objective An abundance of select transcripts and proteins has been found to be dysregulated in blood samples of Machado–Joseph disease (MJD) carriers. Here, we aimed to: (1) identify blood transcriptional changes as potential biomarkers of MJD; (2) correlate levels of differentially expressed blood transcripts with MJD carriers features; and (3 ...
Ana F. Ferreira, Mafalda Raposo, Emily D. Shaw, Louisa Liu, João Vasconcelos, Teresa Kay, Conceição Bettencourt, Maria Luiza Saraiva‐Pereira, Laura Bannach Jardim, Maria do Carmo Costa, Manuela Lima   +10 more
wiley   +1 more source

Mitochondria and Endoplasmic Reticulum Contact Site as a Regulator of Proteostatic Stress Responses in Neurodegenerative Diseases

BioEssays, Volume 47, Issue 7, July 2025.
Recent findings indicate that mitochondria‐associated membranes (MAMs), where the endoplasmic reticulum directly contacts the mitochondria, are a novel microdomain essential for cellular homeostasis, including proteostasis. We summarize the disruption of protein homeostasis and MAM alteration in neurodegenerative diseases, then discuss challenges and ...
Seiji Watanabe, Koji Yamanaka
wiley   +1 more source

Oxidative Stress: Signaling Pathways, Biological Functions, and Disease

MedComm, Volume 6, Issue 7, July 2025.
Oxidative stress causes cellular damage across multiple systems, contributing to neurodegeneration (Alzheimer's, Parkinson's, Huntington's), cancer progression and resistance, cardiovascular diseases (atherosclerosis, heart failure), liver and kidney injury, metabolic disorders (diabetes, obesity), autoimmune diseases, musculoskeletal decline, retinal ...
Sixuan Liu, Jiachen Liu, Yinhuai Wang, Fei Deng, Zebin Deng   +4 more
wiley   +1 more source