The synuclein family and particularly alpha-synuclein takes a central part in etiology and pathogenesis of Parkinson's disease--one of the most common human neurodegenerative diseases. The pathological changes in certain other neurodegenerative diseases are also linked to changes in metabolism and function of alpha-synuclein, hence comprising a new group of diseases--synucleinopathies. The molecular and cellular mechanisms that are involved in the development of neurodegeneration in synucleinopathies are still largely unknown. As a result, the therapeutic approaches to the treatment of synucleinopathies are inadequately tampered. The development of models of neurodegenerative process in laboratory animals plays a crucial role in the study of these molecular mechanisms. Recently a special emphasis was placed on transgenic animal models with modified expression of genes, which mutations are associated with inherited forms of human neurodegenerative diseases. Current review is devoted to the analysis of different models of synucleinopathies as a result of genetic modifications of alpha-synuclein expression.
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Acta Neuropathol Commun
January 2025
Department of Physiology and Pharmacology, Sapienza University of Rome, 00185, Rome, Italy.
The generation of retinal models from human induced pluripotent stem cells holds significant potential for advancing our understanding of retinal development, neurodegeneration, and the in vitro modeling of neurodegenerative disorders. The retina, as an accessible part of the central nervous system, offers a unique window into these processes, making it invaluable for both study and early diagnosis. This study investigates the impact of the Frontotemporal Dementia-linked IVS 10 + 16 MAPT mutation on retinal development and function using 2D and 3D retinal models derived from human induced pluripotent stem cells.
View Article and Find Full Text PDFMol Neurodegener
January 2025
The Picower Institute for Learning and Memory, Cambridge, MA, USA.
Many diseases and disorders of the nervous system suffer from a lack of adequate therapeutics to halt or slow disease progression, and to this day, no cure exists for any of the fatal neurodegenerative diseases. In part this is due to the incredible diversity of cell types that comprise the brain, knowledge gaps in understanding basic mechanisms of disease, as well as a lack of reliable strategies for delivering new therapeutic modalities to affected areas. With the advent of single cell genomics, it is now possible to interrogate the molecular characteristics of diverse cell populations and their alterations in diseased states.
View Article and Find Full Text PDFNat Neurosci
January 2025
Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany.
Our understanding of Alzheimer's disease (AD) has transformed from a purely neuronal perspective to one that acknowledges the involvement of glial cells. Despite remarkable progress in unraveling the biology of microglia, astrocytes and vascular elements, the exploration of oligodendrocytes in AD is still in its early stages. Contrary to the traditional notion of oligodendrocytes as passive bystanders in AD pathology, emerging evidence indicates their active participation in and reaction to amyloid and tau pathology.
View Article and Find Full Text PDFNat Commun
January 2025
Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Amsterdam, The Netherlands.
DOPA Decarboxylase (DDC) has been proposed as a cerebrospinal fluid (CSF) biomarker with increased concentrations in Lewy body disorders (LBDs) and highest levels in patients receiving dopaminergic treatment. Here we evaluate plasma DDC, measured by proximity extension assay, and the effect of dopaminergic treatment in three independent LBD (with a focus on dementia with Lewy bodies (DLB) and Parkinson's disease (PD)) cohorts: an autopsy-confirmed cohort (n = 71), a large multicenter, cross-dementia cohort (n = 1498) and a longitudinal cohort with detailed treatment information (n = 66, median follow-up time[IQR] = 4[4, 4] years). Plasma DDC was not altered between different LBDs and other disease groups or controls in absence of treatment.
View Article and Find Full Text PDFJ Mol Histol
January 2025
Department of Thoracic Surgery, Lung Cancer Diagnosis and Treatment Center of Dalian, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
Malignant tumors are among the major diseases threatening human survival in the world, and advancements in medical technology have led to a steady increase in their detection rates worldwide. Despite unique clinical presentations across the spectrum of malignancies, treatment modalities generally adhere to common strategies, encompassing primarily surgical intervention, radiation therapy, chemotherapy, and targeted treatments. Uncovering the genetic elements contributing to cancer cell proliferation, metastasis, and drug resistance remains a pivotal pursuit in the development of novel targeted therapeutics.
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