During adult neurogenesis, neuronal stem cells differentiate into mature neurons that are functionally integrated into the existing network. One hallmark during the late phase of this neurodifferentiation process is the formation of dendritic spines. These morphological specialized structures form the basis of most excitatory synapses in the brain, and are essential for neuronal communication. Additionally, dendritic spines are affected in neurological disorders, such as Alzheimer's disease or schizophrenia. However, the mechanisms underlying spinogenesis, as well as spine pathologies, are poorly understood. Plasticity-related Gene 5 (PRG5), a neuronal transmembrane protein, has previously been linked to spinogenesis . Here, we analyze endogenous expression of the PRG5 protein in different mouse brain areas, as well as on a subcellular level. We found that native PRG5 is expressed dendritically, and in high abundance in areas characterized by their regenerative capacity, such as the hippocampus and the olfactory bulb. During adult neurogenesis, PRG5 is specifically expressed in a late phase after neuronal cell-fate determination associated with dendritic spine formation. On a subcellular level, we found PRG5 not to be localized at the postsynaptic density, but at the base of the synapse. In addition, we showed that PRG5-induced formation of membrane protrusions is independent from neuronal activity, supporting a possible role in the morphology and stabilization of spines.
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http://dx.doi.org/10.3389/fncel.2022.797588 | DOI Listing |
Alzheimers Dement
December 2024
Merry Life Biomedical Company, Ltd., Tainan City, Taiwan, Taiwan.
Background: Alzheimer's disease (AD) is complex in pathogenesis and related to aging biology, especially in late-onset AD. We identified a novel synthetic curcumin analog TML-6 through the platform of 6 biomarkers of anti-aging, anti-inflammation, and anti-Aβ as the potential AD drug candidate. TML-6 exhibits multi-target effects on AD pathogenesis, including the activation of NrF-2, the regulation of autophagic machinery through mTOR, the inhibition of APP synthesis and reduction of Aβ, the upregulation of ApoE, and the inhibition of microglial activation.
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December 2024
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Background: Anti-amyloid immunotherapies modestly slow disease progression in early symptomatic AD; addition of other therapeutic modalities may be necessary to achieve larger treatment effects. Therapies that directly target tau can potentially produce substantial clinical benefit because the accumulation of insoluble tau protein is strongly correlated with the progression of AD. Which tau therapies are likely to be efficacious, whether or not to combine them with anti-amyloid therapies, and which individuals are most likely to benefit are important unresolved questions that would require multiple parallel design trials to answer.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
School of Medicine, Johns Hopkins University, and Johns Hopkins Bayview Medical Center, Baltimore, MD, USA.
Background: Agitation is a common and disabling symptom of Alzheimer's dementia (AD). Pharmacological treatments are recommended if agitation is not responsive to psychosocial intervention. Citalopram was effective in treating agitation in AD but was associated with cognitive and cardiac risks linked to its R- but not S-enantiomer.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the presence of brain amyloid beta (Aβ) plaques and stages of memory loss, cognitive decline, psychological and psychiatric changes, inability to perform activities of daily living, dementia, and eventually death. Recent evidence demonstrates the slowing of clinical decline with plaque-clearing, anti-Aβ monoclonal antibodies. PRX012 is a humanized monoclonal antibody that targets and clears known pathogenic forms of Aβ in development for subcutaneous (SC) use.
View Article and Find Full Text PDFR Soc Open Sci
January 2025
Department of Biological Sciences, Idaho State University, Pocatello, Idaho, USA.
Millerettidae are a group of superficially lizard-like Permian stem reptiles originally hypothesized as relevant to the ancestry of the reptile crown group, and particularly to lepidosaurs and archosaurs. Since the advent of cladistics, millerettids have typically been considered to be more distant relatives of crown reptiles as the earliest-diverging parareptiles and therefore outside of 'Eureptilia'. Despite this cladistic consensus, some conspicuous features of millerettid anatomy invite reconsideration of their relationships.
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