Progress and Challenges in the Development of PET Ligands to Aid CNS Drug Discovery

Mercier, Joël; Provins, Laurent; Hannestad, Jonas

doi:10.1016/b978-0-12-409547-2.12437-0

Cited by 8 publications

(4 citation statements)

References 313 publications

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“…On one hand, GSK-3β is a GSK-3 isoform, part of the serine/threonine kinase family, known for its important roles in neuron polarity and synapse plasticity. Consequently, there is strong evidence of its implications in the pathological mechanisms of neurodegeneration disease development and the progression of tauopathies associated with AD [ 114 , 115 , 116 , 117 ]. In this context, blood levels of GSK-3β are considerably elevated in AD and MCI patients, which proves its potential as a blood-based AD biomarker [ 105 , 118 ].…”

Section: Blood Biomarkersmentioning

confidence: 99%

Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

2020

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Neurodegeneration is a highly complex process which is associated with a variety of molecular mechanisms related to ageing. Among neurodegenerative disorders, Alzheimer’s disease (AD) is the most common, affecting more than 45 million individuals. The underlying mechanisms involve amyloid plaques and neurofibrillary tangles (NFTs) deposition, which will subsequently lead to oxidative stress, chronic neuroinflammation, neuron dysfunction, and neurodegeneration. The current diagnosis methods are still limited in regard to the possibility of the accurate and early detection of the diseases. Therefore, research has shifted towards the identification of novel biomarkers and matrices as biomarker sources, beyond amyloid-β and tau protein levels within the cerebrospinal fluid (CSF), that could improve AD diagnosis. In this context, the aim of this paper is to provide an overview of both conventional and novel biomarkers for AD found within body fluids, including CSF, blood, saliva, urine, tears, and olfactory fluids.

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Section: Blood Biomarkersmentioning

confidence: 99%

Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

2020

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“…Some of these genes play pivotal roles in neurodegenerative disorders. First of all, we are talking about VCAM1 , a key immune system player that is expressed in endothelial cells in response to cytokines stimulus, for example IL-1 and TNF [ 46 ]. It mediates adhesion of leukocytes including lymphocytes and monocytes.…”

Section: Resultsmentioning

confidence: 99%

The Effect of Meclofenoxate on the Transcriptome of Aging Brain of Nothobranchius guentheri Annual Killifish

Bakhtogarimov

Kudryavtseva

Krasnov

et al. 2022

IJMS

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Annual fish of the genus Nothobranchius are promising models for aging research. Nothobranchius reproduces typical aspects of vertebrate aging, including hallmarks of brain aging. Meclofenoxate (MF) is a well-known compound that can enhance cognitive performance. The drug is prescribed for asthenic conditions, trauma, and vascular diseases of the brain. It is believed that MF is able to delay age-dependent changes in the human brain. However, until now, there has been no study of the MF effect on the brain transcriptome. In the present work, we performed an RNA-Seq study of brain tissues from aged Nothobranchius guentheri, which were almost lifetime administered with MF, as well as young and aged control fish. As expected, in response to MF, we revealed significant overexpression of neuron-specific genes including genes involved in synaptic activity and plasticity, neurotransmitter secretion, and neuron projection. The effect was more pronounced in female fish. In this aspect, MF alleviated age-dependent decreased expression of genes involved in neuronal activity. In both treated and untreated animals, we observed strong aging-associated overexpression of immune and inflammatory response genes. MF treatment did not prevent this effect, and moreover, some of these genes tended to be slightly upregulated under MF treatment. Additionally, we noticed upregulation of some genes associated with aging and cellular senescence, including isoforms of putative vascular cell adhesion molecule 1 (VCAM1), protein O-GlcNAcase (OGA), protein kinase C alpha type (KPCA), prolow-density lipoprotein receptor-related protein 1 (LRP1). Noteworthy, MF treatment was also associated with the elevated transcription of transposons, which are highly abundant in the N. guentheri genome. In conclusion, MF compensates for the age-dependent downregulation of neuronal activity genes, but its effect on aging brain transcriptome still cannot be considered unambiguously positive.

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“…Indeed, unlike the other psychedelics, DMT may bind to the sigma-1 receptor (Fontanilla et al, 2009; Szabo et al, 2016). This receptor is not a GPCR (Mercier et al, 2017), and there is limited evidence on its ability to recruit β-arrestin2 (Moreno et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Synergistic, Multi-level Understanding of Psychedelics: Three Systematic Reviews and Meta-analyses of Their Pharmacology, Neuroimaging and Phenomenology

Shinozuka,

Jerotic,

Mediano

et al. 2023

Preprint

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Serotonergic psychedelics induce altered states of consciousness and have shown potential in treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are currently not fully understood. Here, we provide three systematic reviews and meta-analyses of three hierarchical levels relevant to the effects of psychedelics, i.e., 1) their molecular pharmacology, 2) whole-brain neuroimaging and 3) subjective experience (phenomenology). Our meta-analyses link each of the classic psychedelics (DMT, LSD, and psilocybin) to specific neural fingerprints at each level of this tripartite hierarchy. The results show a highly non-linear relationship between these fingerprints. Overall, the results point to the need for standardising experimental procedures and analysis techniques, as well as for more research on the emergence between different levels of psychedelic effects. Future work could use our tripartite hierarchy framework to investigate the dose-dependent effects of different psychedelics in the same participants.

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Progress and Challenges in the Development of PET Ligands to Aid CNS Drug Discovery

Cited by 8 publications

References 313 publications

Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

The Effect of Meclofenoxate on the Transcriptome of Aging Brain of Nothobranchius guentheri Annual Killifish

Synergistic, Multi-level Understanding of Psychedelics: Three Systematic Reviews and Meta-analyses of Their Pharmacology, Neuroimaging and Phenomenology

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