The future of pharmaceuticals: Artificial intelligence in drug discovery and development

Journal of Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 101248 - 101248

Published: Feb. 1, 2025

Language: Английский

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Exploring the Role of Locus Coeruleus in Alzheimer’s Disease: a Comprehensive Update on MRI Studies and Implications

Current Neurology and Neuroscience Reports, Journal Year: 2023, Volume and Issue: 23(12), P. 925 - 936

Published: Dec. 1, 2023

Abstract Purpose of Review Performing a thorough review magnetic resonance imaging (MRI) studies assessing locus coeruleus (LC) integrity in ageing and Alzheimer’s disease (AD), contextualizing them with current preclinical neuropathological literature. Recent Findings MRI successfully detected LC alterations AD, identifying degenerative phenomena involving this nucleus even the prodromal stages disorder. The degree disruption was also associated severity AD cortical pathology, cognitive behavioral impairment, risk clinical progression. Summary Locus coeruleus-MRI has proved to be useful tool assess central noradrenergic system vivo humans. It allowed test patients experimental hypothesis, thus confirming specific marked involvement its key pathogenetic role. coeruleus-MRI–related data might represent theoretical basis on which start developing drugs target AD.

Language: Английский

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Depression and metabolic connectivity: insights into the locus coeruleus, HF-rTMS, and anxiety

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 2, 2024

The use of repetitive Transcranial Magnetic Stimulation (rTMS) in treating major depressive disorder (MDD) is increasingly being explored precision medicine. However, there's a notable lack understanding the underlying neurobiological effects, which limits our ability to correlate specific imaging features with treatment efficacy. As one possible mechanism, clinical research has already shown that MDD, lower norepinephrine release locus coeruleus (LC) triggers symptoms, and pharmacological approaches block reuptake boost its levels, easing depression. Surprisingly, LC not received more pronounced focus contemporary rTMS research. This study investigates role MDD response high-frequency (HF)-rTMS using 18FDG-PET imaging. We compared metabolic connectivity between patients (n = 43) healthy controls 32). Additionally, we evaluated predictive value for HF-rTMS outcomes examined post-treatment changes connectivity. Our findings revealed significant differences controls. Baseline did predict outcomes. analyses showed correlation improved attenuation regions associated cognitive control default mode network. Notably, reduction state anxiety moderated this relationship, highlighting efficacy treatment. suggest connectivity, influenced by may be crucial efficacy, offering further insights personalized strategies.

Language: Английский

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Locus coeruleus neuromelanin, cognitive dysfunction, and brain metabolism in multiple system atrophy

Journal of Neurology, Journal Year: 2025, Volume and Issue: 272(3)

Published: Feb. 11, 2025

Abstract Background Cognitive dysfunction is increasingly recognized in multiple system atrophy (MSA). Locus coeruleus (LC) integrity associated with cognitive performance both healthy controls (HC) and neurodegenerative conditions such as Parkinson’s disease (PD). Furthermore, cortical glucose hypometabolism impaired MSA. However, knowledge about LC sub-regional degeneration its association metabolism lacking. Objective To investigate involvement impairment brain Methods Eleven MSA, eighteen PD, HC participants were included the study. Neuromelanin-sensitive MRI was used to determine rostral, middle caudal neuromelanin signals. Brain investigated [ 18 F]Fluorodeoxyglucose PET (FDG-PET). The Montreal Assessment (MoCA) a measure of global cognition. Results Middle signal significantly reduced MSA t (43) = 3.70, corrected- p 0.004] PD 2.63, 0.041] compared HC, while only 2.82, 0.030]. In decreased rostral lower MoCA scores ( ρ 0.760, 0.006) which, turn, frontal cortex metabolism. An between found exploratory analyses. Conclusion Loss parts being targeted. Rostral loss scores. This pathophysiological link should be further noradrenergic transmission amenable pharmacological manipulation.

Language: Английский

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Different Patterns of Locus Coeruleus MRI Alteration in Alzheimer’s and Dementia with Lewy Bodies

Current Alzheimer Research, Journal Year: 2023, Volume and Issue: 20(4), P. 277 - 288

Published: April 1, 2023

The integrity of Locus Coeruleus can be evaluated in vivo using specific Magnetic Resonance Imaging sequences. While this nucleus has been shown to degenerated both post-mortem and studies Alzheimer's Disease, for other neurodegenerative dementias such as Dementia with Lewy Bodies only ex-vivo.To evaluate the through patients suffering from explore possible differences alterations occurring Dementia.Eleven 35 were recruited underwent Imaging, along 52 cognitively intact, age-matched controls. Images analyzed applying an already developed template-based approach; signal was expressed Contrast Ratio parameter, a locoregional analysis performed.Both groups showed significantly lower values when compared A different pattern spatial involvement found; affected by bodies global bilateral Coeruleus, whereas more likely localized rostral part left nucleus.Magnetic successfully detects widespread degeneration Bodies. Further studies, larger cohorts earlier stages disease, are needed better disclose potential diagnostic prognostic role neuroradiological tool.

Language: Английский

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The role of brain noradrenaline in Alzheimer's disease: Implications for a precision medicine-oriented approach

Elsevier eBooks, Journal Year: 2023, Volume and Issue: unknown, P. 526 - 539

Published: May 26, 2023

Language: Английский

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Locus coeruleus MRI contrast, cerebral perfusion, and plasma Alzheimer’s disease biomarkers in older adults

Neurobiology of Aging, Journal Year: 2024, Volume and Issue: 147, P. 12 - 21

Published: Nov. 27, 2024

Language: Английский

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