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The Search for a Universal Treatment for Defined and Mixed Pathology Neurodegenerative Diseases.
Int J Mol Sci
December 2024
Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada.
The predominant neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, dementia with Lewy Bodies, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are rarely pure diseases but, instead, show a diversity of mixed pathologies. At some level, all of them share a combination of one or more different toxic biomarker proteins: amyloid beta (Aβ), phosphorylated Tau (pTau), alpha-synuclein (αSyn), mutant huntingtin (mHtt), fused in sarcoma, superoxide dismutase 1, and TAR DNA-binding protein 43. These toxic proteins share some common attributes, making them potentially universal and simultaneous targets for therapeutic intervention.
View Article and Find Full Text PDFThe perisomatic region of cortical pyramidal neurons (PNs) integrates local and long-range inputs and regulates firing.This domain receives GABAergic inputs from cholecystokinin (CCK)- and parvalbumin (PV)-expressing basket cells (BCs) but how synaptic contacts are established is unclear. Neuron-glial related cell adhesion molecule (NrCAM) is a homophilic transmembrane protein that binds the scaffold protein Ankyrin B.
View Article and Find Full Text PDFAstrocytes initiate autophagic flux and maintain cell viability after internalizing non-active native extracellular α-synuclein.
Mol Cell Neurosci
December 2024
Biology Department, University of Hartford, 200 Bloomfield Avenue, West Hartford, CT 06117, United States of America. Electronic address:
Astrocytes are tasked with regulating the synaptic environment. Early stages of various neurodegenerative diseases are characterized by synapse loss, and astrocytic atrophy and dysfunction has been proposed as a possible cause. α-Synuclein (αS) is a highly expressed neuronal protein located in the synapse that can be released in the extracellular space.
View Article and Find Full Text PDFCerebrospinal fluid synaptic biomarker changes in bipolar disorder - A longitudinal case-control study.
J Affect Disord
August 2024
Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Department Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark.
Background: This exploratory study investigated cerebrospinal fluid (CSF) synaptic protein biomarkers in bipolar disorder (BD), aiming to highlight the neurobiological basis of the disorder. With shared cognitive impairment features between BD and Alzheimer's disease, and considering increased dementia risk in BD patients, the study explores potential connections.
Methods: Fifty-nine well-characterized patients with BD and thirty-seven healthy control individuals were examined and followed for one year.
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