The protein molecules must fold into unique conformations to acquire functional activity. Misfolding, aggregation, and deposition of proteins in diverse organs, the so-called "protein misfolding disorders (PMDs)", represent the conformational diseases with highly ordered assemblies, including oligomers and fibrils that are linked to neurodegeneration in brain illnesses such as cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Recent studies have revealed several aspects of brain pathology in CAA and AD, but both the classification and underlying mechanisms need to be further refined. MicroRNAs (miRNAs) are critical regulators of gene expression at the post-transcriptional level. Increasing evidence with the advent of RNA sequencing technology suggests possible links between miRNAs and these neurodegenerative disorders. To provide insights on the small RNA-mediated regulatory circuitry and the translational significance of miRNAs in PMDs, this review will discuss the characteristics and mechanisms of the diseases and summarize circulating or tissue-resident miRNAs associated with AD and CAA.
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http://dx.doi.org/10.1007/s12017-019-08568-0 | DOI Listing |
Sci Adv
January 2025
Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Several human disorders, including Alzheimer's disease (AD), are characterized by the aberrant formation of amyloid fibrils. In many cases, the amyloid core is flanked by disordered regions, known as fuzzy coat. The structural properties of fuzzy coats, and their interactions with their environments, however, have not been fully described to date.
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Antiamyloid antibody treatments modestly slow disease progression in mild dementia due to AD. Emerging evidence shows that homeostatic dysregulation of the brain immune system, especially that orchestrated by microglia, plays an important role in disease onset and progression.
View Article and Find Full Text PDFChembiochem
January 2025
China Pharmaceutical University, Department of Pharmaceutical Science, #639 Longmian Dadao, Jiangning District, 211198, Nanjing, CHINA.
Alzheimer's disease (AD) is a significant neurodegenerative disorder primarily affecting individuals over the age of 65. It is characterized by impairments in memory, thinking, analytical judgment, visuospatial recognition, and mood. In recent years, the development of protein and peptide drugs targeting amyloid-beta (Aβ) has gained momentum, with several therapies entering clinical trials and even receiving marketing approval.
View Article and Find Full Text PDFBrain
January 2025
U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Neuropresage Team; INSERM, University of Caen Normandy; GIP Cyceron, 14000 Caen, France.
Curing Alzheimer's disease remains hampered by an incomplete understanding of its pathophysiology and progression. Exploring dysfunction in medial temporal lobe networks, particularly the anterior-temporal (AT) and posterior-medial (PM) systems, may provide key insights, as these networks exhibit functional connectivity alterations along the entire Alzheimer's continuum, potentially influencing disease propagation. However, the specific changes in each network and their clinical relevance across stages are not yet fully understood.
View Article and Find Full Text PDFJ Neurol
January 2025
Department of Central laboratory, Xuanwu Hospital of Capital Medical University, Beijing, 100053, P.R. China.
Background: Circadian disruptions are increasingly recognized in Alzheimer's disease (AD) patients and may influence disease onset and progression. This study examines how AD pathology affects blood-borne factors that regulate circadian rhythms.
Methods: Eighty-five participants from the Sino Longitudinal Study on Cognitive Decline were enrolled: 35 amyloid-beta negative normal controls (Aβ- NCs), 23 amyloid-beta positive normal controls (Aβ+ NCs), 15 patients with amnestic mild cognitive impairment (aMCI), and 12 with Alzheimer's disease dementia (ADD).
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