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Characteristics of TSPO expression in marmoset EAE.
J Neuroinflammation
January 2025
Viral Immunology Section, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Building 10, Room 5C103, 10 Center Drive, Bethesda, MD, 20892-1400, USA.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) and is a leading non-traumatic cause of disability in young adults. The 18 kDa Translocator Protein (TSPO) is a mitochondrial protein and positron emission tomography (PET)-imaging target that is highly expressed in MS brain lesions. It is used as an inflammatory biomarker and has been proposed as a therapeutic target.
View Article and Find Full Text PDFLight chain Split Luciferase assay implicates pathological NOTCH3 thiol reactivity in inherited cerebral small vessel disease.
J Biol Chem
January 2025
Departments of Neurology, University of Michigan, Ann Arbor, MI 48109; Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109; Neurology Service, VA Ann Arbor Healthcare System, Department of Veterans Affairs, Ann Arbor, MI 48105. Electronic address:
Stereotyped mutations in NOTCH3 drive CADASIL, the leading inherited cause of stroke and vascular dementia. The vast majority of these mutations result in alterations in the number of cysteines in the gene product. However, non-cysteine altering pathogenic mutations have also been identified, making it challenging to discriminate pathogenic from benign NOTCH3 sequence variants.
View Article and Find Full Text PDFThe Microbiota-Gut-Brain Axis: Key Mechanisms Driving Glymphopathy and Cerebral Small Vessel Disease.
Life (Basel)
December 2024
Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman P.O. Box 346, United Arab Emirates.
The human microbiota constitute a very complex ecosystem of microorganisms inhabiting both the inside and outside of our bodies, in which health maintenance and disease modification are the main regulatory features. The recent explosion of microbiome research has begun to detail its important role in neurological health, particularly concerning cerebral small vessel disease (CSVD), a disorder associated with cognitive decline and vascular dementia. This narrative review represents state-of-the-art knowledge of the intimate, complex interplay between microbiota and brain health through the gut-brain axis (GBA) and the emerging role of glymphatic system dysfunction (glymphopathy) and circulating cell-derived microparticles (MPs) as mediators of these interactions.
View Article and Find Full Text PDFProduction of Amyloid-β in the Aβ-Protein-Precursor Proteolytic Pathway Is Discontinued or Severely Suppressed in Alzheimer's Disease-Affected Neurons: Contesting the 'Obvious'.
Genes (Basel)
January 2025
Division of Molecular Medicine, Children's Hospital, Boston, MA 02115, USA.
A notion of the continuous production of amyloid-β (Aβ) via the proteolysis of Aβ-protein-precursor (AβPP) in Alzheimer's disease (AD)-affected neurons constitutes both a cornerstone and an article of faith in the Alzheimer's research field. The present Perspective challenges this assumption. It analyses the relevant empirical data and reaches an unexpected conclusion, namely that in AD-afflicted neurons, the production of AβPP-derived Aβ is either discontinued or severely suppressed, a concept that, if proven, would fundamentally change our understanding of the disease.
View Article and Find Full Text PDFIntegrated analysis of chromatin and transcriptomic profiling of the striatum after cerebral hypoperfusion in mice.
BMC Genomics
January 2025
Department of Vascular Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Background: Vascular cognitive impairment (VCI) is a significant contributor to dementia, yet the precise mechanisms underlying the cognitive decline associated with chronic cerebral hypoperfusion (CCH) remain unclear. This study investigated the molecular and epigenetic changes in the striatum, a brain region critical for motor function and cognition, following chronic hypoperfusion using a bilateral common carotid artery stenosis (BCAS) model in mice.
Methods: RNA-seq was utilized to identify differentially expressed genes (DEGs) associated with hypoperfusion.
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