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Parkinson's disease (PD) is a highly heterogeneous neurodegenerative disorder. This study aimed to identify different patterns of early brain degeneration in PD patients and investigate their clinical relevance. 179 early-stage PD patients and 115 healthy controls were included. We assessed cortical morphology, white matter microstructure, and subcortical iron metabolism using multimodal magnetic resonance imaging and employed clustering techniques to identify subtypes. Two subtypes were identified: the early-deterioration subtype, characterized by fronto-temporal atrophy, parietal thickening, widespread reductions in fractional anisotropy (FA) values, and increased subcortical iron content, which exhibited more severe baseline symptoms and a trend of faster memory decline; and the early-compensatory subtype, characterized by rostral middle frontal atrophy, parietal-occipital thickening, increased FA values, and normal iron content, which exhibited milder symptoms initially but experienced faster progression of both motor and non-motor symptoms. These discoveries provided new insights into disease heterogeneity and facilitated the exploration of early neurodegenerative mechanisms.
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http://dx.doi.org/10.1038/s41531-025-00975-4 | DOI Listing |
J Integr Neurosci
August 2025
Institute of Neuroscience and Third Affiliated Hospital, Zhengzhou University, 450052 Zhengzhou, Henan, China.
Background: Germinal matrix hemorrhage (GMH) is a common complication of premature infants with lifelong neurological consequences. Inflammation-mediated blood-brain barrier (BBB) disruption has been implicated as a main mechanism of secondary brain injury after GMH. The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a crucial role in inflammation, yet its involvement in GMH pathophysiology remains unclear.
View Article and Find Full Text PDFBrain
September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Guangdong Provincial Key Laboratory of Non-human Primate Research, Guangdong-Hong Kong-Macau Institute of CNS Rege
Abnormal accumulation of TAR DNA-binding protein-43 (TDP-43) is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Small interfering RNAs (siRNAs) targeting TDP-43 offer potential therapeutic strategies for these diseases. However, efficient and safe delivery of siRNAs to the central nervous system (CNS) remains a critical challenge.
View Article and Find Full Text PDFNeuropeptides
September 2025
Department of Physiology and Cell Biology, The National Institute for Biotechnology in the Negev, and the School of Brain Sciences and Cognition, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Despite extensive research into Alzheimer's disease (AD), few therapeutic strategies have successfully addressed its core pathology at the synaptic level. Small peptides represent a promising class of therapeutic agents capable of modulating key molecular pathways involved in amyloid toxicity, tau hyperphosphorylation, and synaptic degeneration. Their unique ability to cross biological barriers, interact with intracellular targets, and be modified for enhanced stability positions them as viable candidates for next-generation treatments targeting cognitive decline in AD.
View Article and Find Full Text PDFFree Radic Biol Med
September 2025
Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, The First Affiliated Hospital of Guangxi Medical University,Nanning, Guangxi 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education,
Background: The second most common cause of autosomal recessive early-onset Parkinson's disease (PD) can be attributed to mutations in the PINK1 gene, malfunction of the mitochondria is the key pathological mechanism. Bre1 encodes an E3 ubiquitin ligase, with the discovery of Bre1's role in repairing mitochondrial damage, further investigation into its implications for PD is warranted.
Methods: We used the PINK1B9 drosophila melanogaster as the PD model.
Toxicon
September 2025
Department of Pathology, College of Medicine, King Khalid University, P.O. 641, Abha, 61421, Saudi Arabia; Department of Forensic Medicine and Clinical Toxicology, Mansoura University, Egypt.
Titanium dioxide nanoparticles (TiO-NPs) are used in the production of various industrial and commercial products and reported to cause neurotoxicity in Sprague Dawley rats. Fortunellin (FRN) is a potent flavonoid with diverse biological properties. This research experiment was performed to explore the protective role FRN against TiO-NPs induced brain damage.
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