Results 41 to 50 of about 16,368 (183)

C9orf72 intermediate repeats are associated with corticobasal degeneration, increased C9orf72 expression and disruption of autophagy [PDF]

, 2019
Microsatellite repeat expansion disease loci can exhibit pleiotropic clinical and biological effects depending on repeat length. Large expansions in C9orf72 (100s–1000s of units) are the most common genetic cause of amyotrophic lateral sclerosis (ALS ...
Schellenberg, Gerard D., Lee, Virginia M-Y, Gaig, Carles, Van Deerlin, Vivianna M., Dickson, Dennis W., Schellenberg, Gerard D, Trojanowski, John Q., Ghetti, Bernardino, Mok, Kin Y, Seeley, William W., Ling, Shuo-Chien, Roeber, Sigrun, Morris, Christopher M, Lee, Virginia M.Y., Lee, Virginia M.-Y., Lee, Edward B., Ling, Helen, Kretzschmar, Hans, Gearing, Marla, White, Charles L, Troncoso, Juan C, Seeley, William W, Lee, Edward B, Trojanowski, John Q, Cali, Christopher P., Troakes, Claire, McLean, Catriona A., Miller, Bruce L, Tai, Yee Kit, Cali, Christopher P, White, Charles L., Ling, Shuo Chien, Vonsattel, Jean Paul G., Van Deerlin, Vivianna M, Morris, Christopher M., Vonsattel, Jean Paul G, Ho, Wan Yun, Mok, Kin Y., McLean, Catriona A, Troncoso, Juan C., Miller, Bruce L., Dickson, Dennis W, Patino, Maribel, Troakes, Claire; id_orcid   +43 more
core   +1 more source

Concomitant gain and loss of function pathomechanisms in C9ORF72 amyotrophic lateral sclerosis

Life Science Alliance, 2021
Axonal trafficking deficits and neurodegeneration in C9ORF72 motoneurons are mediated by GOF and LOF mechanisms with RNA foci and DPRs as upstream events, whereas DNA damage appears downstream.
Arun Pal, Benedikt Kretner, Masin Abo-Rady, Hannes Glaβ, Banaja P Dash, Marcel Naumann, Julia Japtok, Nicole Kreiter, Ashutosh Dhingra, Peter Heutink, Tobias M Böckers, René Günther, Jared Sterneckert, Andreas Hermann   +13 more
doaj   +1 more source

Autophagy and neurodegeneration: Unraveling the role of C9ORF72 in the regulation of autophagy and its relationship to ALS-FTD pathology. [PDF]

, 2023
The proper functioning of the cell clearance machinery is critical for neuronal health within the central nervous system (CNS). In normal physiological conditions, the cell clearance machinery is actively involved in the elimination of misfolded and ...
Diab, Rim, Rim Diab, Pilotto, Federica, Smita Saxena, Federica Pilotto, Saxena, Smita   +5 more
core   +2 more sources

Evaluation of Digital Technologies for Home‐Based Assessment in People With Amyotrophic Lateral Sclerosis

Annals of Clinical and Translational Neurology, EarlyView.
ABSTRACT Objective Digital technologies hold promise for transforming healthcare by enhancing personalized treatments and offer valuable opportunities to improve patient care. Here, we evaluated several novel, self‐administered, home‐based, digital endpoints for their association with corresponding conventional standard clinical measures (primary) in ...
Arne Mueller, Vanessa Vallejo, Mónica Povedano Panadés, Orla Hardiman, Véronique Danel‐Brunaud, Senda Ajroud‐Driss, Philippe Couratier, Jeremy Shefner, Anna Gokey, Mike DiCesare, Erin Lennox, Jens Praestgaard, Lucie Brujin, Peggy Allred, Ram Miller   +14 more
wiley   +1 more source

Clinical and Imaging Features of Sporadic and Genetic Frontotemporal Lobar Degeneration TDP‐43 A and B

Annals of Clinical and Translational Neurology
Objective Certain frontotemporal lobar degeneration subtypes, including TDP‐A and B, can either occur sporadically or in association with specific genetic mutations.
Sean Coulborn, Rhiana Schafer, Ashlin R. K. Roy, Andrzej Sokolowski, Noah G. Cryns, Dana Leichter, Argentina Lario Lago, Eliana Marisa Ramos, Yann Cobigo, Salvatore Spina, Lea T. Grinberg, Daniel H. Geschwind, Maria L. Gorno‐Tempini, Joel H. Kramer, Howard J. Rosen, Bruce L. Miller, William W. Seeley, David C. Perry   +17 more
doaj   +1 more source

Cognitive and Neuroimaging Divergence Between Juvenile and Adult FUS Amyotrophic Lateral Sclerosis

Annals of Clinical and Translational Neurology, EarlyView.
ABSTRACT Objective Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive motor neuron degeneration. Fused in sarcoma (FUS)‐associated juvenile ALS (jALS) represents a distinct and aggressive subgroup with rapid deterioration and poor prognosis.
Alexandra V. Jürs, Marcel Naumann, Annaliis Lehto, Hanna Schön, Jens Kurth, Johannes Prudlo, Andreas Hermann, Elisabeth Kasper   +7 more
wiley   +1 more source

Structural Polymorphism of polyG Inclusions Revealed by In Situ Cryo‐Electron Tomography

Advanced Science, EarlyView.
Correlative cryo‐electron tomography in primary cortical neurons and NIID mouse brain tissue reveals that polyG inclusions are interconnected ribbon‐like assemblies rather than canonical amyloid fibrils. Multiple compartment‐specific ribbon states show distinct 26S proteasome accessibility, while cytoplasmic ribbons contact and deform ER‐like ...
Yunwen Qian, Yalan Wan, Chen Chen, Xiaoyu Zheng, Wenjing Du, Junhan Yang, Zhihao Quan, Biyu Yang, Jiaxi Yu, Jie Zheng, Zhaoxia Wang, Jianwen Deng, Qiang Guo   +12 more
wiley   +1 more source

PolyG Fibrils Coalesce Into Nuclear Ribbons That Engage Proteostasis Machinery in Neuronal Intranuclear Inclusion Disease

Advanced Science, EarlyView.
In NIID, expanded NOTCH2NLC repeats give rise to nuclear polyG inclusions. Tracer‐guided in situ cryo‐electron tomography enables cross‐scale structural analysis from mouse brain to native neuronal nuclei, revealing dense‐core/peripheral‐halo inclusions built from compact polyG ribbons.
Hui Dong, Yongcheng Pan, Zhiyao Tang, Yuxuan Yao, Guicong Zhang, Junpu Wang, Haonan Xiao, Yun Tian, Beisha Tang, Dan Li, Qiang Guo, Ruijun Tian, Qiong Liu, Cong Liu   +13 more
wiley   +1 more source

A Blood‐Derived Factor Rescues ALS: Platelet Factor 4 Activates OPTN‐Dependent Autophagy to Clear SOD1 Aggregates Independently of PINK1

Advanced Science, EarlyView.
Systemic platelet factor 4 (PF4) is significantly depleted in amyotrophic lateral sclerosis (ALS). Peripheral PF4 replenishment restores central proteostasis by driving OPTN‐dependent, PINK1‐independent selective autophagy in motor neurons. This intervention effectively clears toxic SOD1 aggregates, blunts glial activation, and preserves neuromuscular ...
Qingjian Xie, Yanbo Zhu, Wenhua Jiang, Haobo Xie, Yaojia Li, Mengjie Hu, Kezheng Li, Huan Yu, Yixuan Pan, Chaoyi Jiang, Xueqin Song, Dongsheng Fan, Binbin Deng   +12 more
wiley   +1 more source

Optimized Cas9‐Enriched Nanopore Sequencing and Analysis Workflow for Clinical Diagnosis of Repeat Expansion Disorders

Advanced Science, EarlyView.
An optimized Cas9‐enriched nanopore sequencing workflow, combined with STRiker, enables simultaneous analysis of disease‐associated STR loci from patient blood. The nCATS–STRiker workflow detects repeat expansions, de novo repeat motifs, interruption patterns, and methylation in a single assay, improving the genetic diagnosis of previously undiagnosed ...
Seungbok Lee, Chanju Jung, Minjeong Kim, Narae Kim, Gue‐Ho Hwang, Soon‐Tae Lee, Kon Chu, Sang Kun Lee, Han‐Joon Kim, Jong‐Hee Chae, Sangsu Bae, Jangsup Moon   +11 more
wiley   +1 more source