Objective: To explore longitudinal changes in brain activity in patients with Parkinson disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) using task-based functional MRI (fMRI).
Methods: A total of 112 individuals were scanned 1 year apart while performing a unimanual grip force task: 46 PD, 13 MSA, 19 PSP, and 34 healthy controls. The outcome measure was percent signal change in prespecified regions of interest: putamen, primary motor cortex (M1), supplementary motor area (SMA), and superior motor regions of the cerebellum (lobules V-VI).
Results: Patients with PD showed a decline in functional activity over the course of 1 year in the putamen and M1 compared to controls. Changes after 1 year in MSA were exclusively extrastriatal, and included a reduction in functional activity in M1, SMA, and superior cerebellum. In PSP, all regions of interest were less active at 1 year compared to baseline. The functional activity of these regions did not change in the control group.
Conclusions: We provide evidence using task-based fMRI for cortical and striatal functional deterioration in PD over a 1-year period of time. Results also describe more widespread and unique patterns of functional changes in MSA and PSP compared to PD, suggesting distinct rates of disease progression in parkinsonian disorders that may assist in future clinical studies testing the potential efficacy of disease-modifying therapies.
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http://dx.doi.org/10.1212/WNL.0000000000002985 | DOI Listing |
J Clin Invest
January 2025
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Ischemic stroke is a major cause of adult disability. Early treatment with thrombolytics and/or thrombectomy can significantly improve outcomes; however, following these acute interventions, treatment is limited to rehabilitation therapies. Thus, the identification of therapeutic strategies that can help restore brain function in the post-acute phase remains a major challenge.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
Lysine demethylases (KDMs) catalyze the oxidative removal of the methyl group from histones using earth-abundant iron and the metabolite 2-oxoglutarate (2OG). KDMs have emerged as master regulators of eukaryotic gene expression and are novel drug targets; small-molecule inhibitors of KDMs are in the clinical pipeline for the treatment of human cancer. Yet, mechanistic insights into the functional heterogeneity of human KDMs are limited, necessitating the development of chemical probes for precision targeting.
View Article and Find Full Text PDFGM Crops Food
December 2025
School of Life Science, Henan University, Kaifeng, Henan, People's Republic of China.
Malic acid markedly affects watermelon flavor. Reducing the malic acid content can significantly increase the sweetness of watermelon. An effective solution strategy is to reduce watermelon malic acid content through molecular breeding technology.
View Article and Find Full Text PDFAnal Chem
January 2025
State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, PR China.
The development of intelligent nanotheranostic technology that integrates diagnostic and therapeutic functions holds great promise for personalized nanomedicine. However, most of the nanotheranostic agents exhibit "always-on" properties and do not involve an amplification step, which may largely limit imaging contrast and restrict therapeutic efficacy. Herein, we construct a novel nanotheranostic platform (Hemin/DHPs/PDA@CuS nanocomposite) by assembling DNA hairpin probes (DHPs) and hemin on the surface of PDA@CuS nanosheets that enables amplified fluorescence imaging and activatable chemodynamic therapy (CDT) of tumors.
View Article and Find Full Text PDFAppl Biochem Biotechnol
January 2025
Department of Internal Medicine-Cardiovascular, Guangzhou Twelfth People's Hospital, No.1, Tianqiang Road, Tianhe District, Guangzhou City, Guangdong Province, 510620, China.
Myocardial infarction (MI) is a coronary artery-related disease that seriously threatens human life and is the leading cause of sudden death worldwide, where a lack of nutrients and oxygen leads to an inflammatory response and death of cardiomyocytes. Ferroptosis is a form of non-apoptotic cell death associated with metabolic dysfunction, resulting in abnormal breakdown of glutamine and iron-dependent accumulation of reactive oxygen species (ROS) during metabolism. However, the molecular mechanism of ferroptosis in the pathogenesis of MI and the function of Klotho and KRAS on ferroptosis during MI remain unclear.
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