Results 31 to 40 of about 57,121 (194)

Antipsychotic olanzapine-induced misfolding of proinsulin in the endoplasmic reticulum accounts for atypical development of diabetes

eLife, 2020
Second-generation antipsychotics are widely used to medicate patients with schizophrenia, but may cause metabolic side effects such as diabetes, which has been considered to result from obesity-associated insulin resistance.
Satoshi Ninagawa, Seiichiro Tada, Masaki Okumura, Kenta Inoguchi, Misaki Kinoshita, Shingo Kanemura, Koshi Imami, Hajime Umezawa, Tokiro Ishikawa, Robert B Mackin, Seiji Torii, Yasushi Ishihama, Kenji Inaba, Takayuki Anazawa, Takahiko Nagamine, Kazutoshi Mori   +15 more
doaj   +1 more source

Unraveling 4‐Phenylbutyrate's Therapeutic Role in SLC6A1 Disorders: Pharmacochaperoning Over HDAC Inhibition

Annals of Clinical and Translational Neurology, EarlyView.
ABSTRACT Objective Variants in SLC6A1, encoding the GABA transporter 1 (GAT‐1), cause epilepsy, autism spectrum disorder, and developmental delay via loss of GABA uptake, impaired trafficking, and ER retention. We previously found that 4‐Phenylbutyrate (PBA), an FDA‐approved drug, restores GABA uptake and reduces seizures in SLC6A1‐related disorders ...
Melissa B. DeLeeuw, Karishma Randhave, Ekta Anand, Ziang (Debbie) Song, Wangzhen Shen, Jing‐Qiong Kang   +5 more
wiley   +1 more source

Engineered Nanoparticle-Protein Interactions Influence Protein Structural Integrity and Biological Significance

Nanomaterials, 2022
Engineered nanoparticles (ENPs) are artificially synthesized particles with unique physicochemical properties. ENPs are being extensively used in several consumer items, elevating the probability of ENP exposure to biological systems.
Surabhi Jaiswal, Amit Manhas, Alok Kumar Pandey, Smriti Priya, Sandeep K. Sharma   +4 more
doaj   +1 more source

Neurochemical Endpoints to Inform Early‐Stage Trials of Spinocerebellar Ataxia 2 and 3 in a Multisite Setting

Annals of Clinical and Translational Neurology, EarlyView.
ABSTRACT Objective Neurochemical levels measured by brain MR spectroscopy (MRS) have been proposed as endpoints for clinical trials in early‐stage spinocerebellar ataxia (SCA) trials. We tested their trial‐readiness by quantifying neurochemicals in three affected brain regions in early‐stage cohorts of SCA2 and SCA3, examining their reproducibility in ...
James M. Joers, Yaqiao Wei, Dinesh K. Deelchand, Adam Berrington, Young Woo Park, Guita Banan, Michal Povazan, Jens T. Rosenberg, André J. W. van der Kouwe, Tetsuo Ashizawa, Khalaf O. Bushara, Chiadi U. Onyike, Sub H. Subramony, Jeremy D. Schmahmann, Brian J. Soher, Peter B. Barker, Thomas H. Mareci, Eva‐Maria Ratai, Lynn E. Eberly, Gülin Öz   +19 more
wiley   +1 more source

Characterizing Cutaneous α‐Synuclein Deposition and Seeding Activity in Parkinson's Disease Subtypes

Annals of Clinical and Translational Neurology, EarlyView.
ABSTRACT Objective Cutaneous phosphorylated α‐synuclein (p‐syn) and α‐synuclein seeding activity are promising biomarkers for Parkinson's disease (PD), but their clinical value remains uncertain due to disease heterogeneity. This study evaluates these two biomarkers in PD patients to inform phenotype‐specific diagnosis and disease severity assessment ...
Yuting Jin, Tianyuan Yang, Minglei Liu, Haiyang Luo, Jing Yuan, Ke Zhang, Xinsheng Han, Jing Yang, Yuming Xu   +8 more
wiley   +1 more source

α-Synuclein oligomers form by secondary nucleation

Nature Communications
Oligomeric species arising during the aggregation of α-synuclein are implicated as a major source of toxicity in Parkinson’s disease, and thus a major potential drug target.
Catherine K. Xu, Georg Meisl, Ewa A. Andrzejewska, Georg Krainer, Alexander J. Dear, Marta Castellana-Cruz, Soma Turi, Irina A. Edu, Giorgio Vivacqua, Raphaël P. B. Jacquat, William E. Arter, Maria Grazia Spillantini, Michele Vendruscolo, Sara Linse, Tuomas P. J. Knowles   +14 more
doaj   +1 more source

Modeling Progressive Brain Volume Losses in Chronic Moderate Severe Traumatic Brain Injury: Extensive, but Attenuating

Annals of Clinical and Translational Neurology, EarlyView.
ABSTRACT Objective Progressive brain atrophy has now been widely observed in the chronic stages of moderate–severe traumatic brain injury (msTBI), but there is only coarse information regarding its prevalence and magnitude, and whether rate of atrophy accelerates or attenuates across time. We examined these questions in a Canadian inception cohort from
Robin E. A. Green, Brenda Colella, Alana Changoor, David J. Mikulis, Adrienne Li, Kadeen Johns, Georges A. Monette   +6 more
wiley   +1 more source

Identification of potent high-affinity secondary nucleation inhibitors of Aβ42 aggregation from an ultra-large chemical library using deep docking

Molecular Systems Biology
Alzheimer’s disease is characterized by the aggregation of the Aβ peptide into amyloid fibrils. According to the amyloid hypothesis, pharmacologically targeting Aβ aggregation could result in disease-modifying treatments. The identification of inhibitors
Michaela Brezinova, Z Faidon Brotzakis, Robert I Horne, Vaidehi Roy Chowdhury, Rebecca C Gregory, Yuqi Bian, Alicia González Díaz, Francesco Gentile, Michele Vendruscolo   +8 more
doaj   +1 more source

Conformational Switching of Proteins on Material Surfaces Enabled by Peptide‐Oriented Adsorption

Advanced Functional Materials, EarlyView.
Responsive biointerfaces could be achieved using conformationally responsive proteins; however, their interconversion can be lost upon surface adsorption. Herein, we demonstrate that the incorporation a Au binding peptide into calmodulin allows for binding control on Au wherein the protein retains conformational switching. This capability was confirmed
Sakthirupini Ramamurthy, Kyle B. Meerbott, Lorenzo Travaglini, Garima S. Dobhal, Artur Sawicki, Marc R. Knecht, Tiffany R. Walsh, Dominic J. Glover   +7 more
wiley   +1 more source

Aggregation of the amyloid-β peptide (Aβ40) within condensates generated through liquid–liquid phase separation

Scientific Reports
The deposition of the amyloid-β (Aβ) peptide into amyloid fibrils is a hallmark of Alzheimer’s disease. Recently, it has been reported that some proteins can aggregate and form amyloids through an intermediate pathway involving a liquid-like condensed ...
Owen M. Morris, Zenon Toprakcioglu, Alexander Röntgen, Mariana Cali, Tuomas P. J. Knowles, Michele Vendruscolo   +5 more
doaj   +1 more source