Samantha Louise McLean

ESCRT-I Inhibition Protects against NMDAR Hypofunction and Restores Synaptic Homeostasis in a Cellular Model of Schizophrenia

Mohamed Shalaby, Vincenzo Prato, Jacobo Elíes, Nikita Gamper et autres

N-methyl-D-aspartate receptor (NMDAR) hypofunction is a central pathophysiological mechanism in schizophrenia, yet direct NMDAR potentiation has shown limited clinical benefit, potentially because it fails to address deficits in receptor trafficking and surface stability. The endosomal sorting complexes required for transport (ESCRT) machinery …

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Are depot antipsychotics ever self-tapering? Exploring the discontinuation of long-acting injectable psychosis drugs and those with delayed onset through in silico modelling

James Richard O’Neill, Samantha Louise McLean, David M Taylor, Mark Horowitz

ABSTRACT Background and Hypothesis Reducing and stopping antipsychotic medications can have longer-term positive outcomes for some patients. Despite common wisdom, abrupt discontinuation of several long-acting injectable (LAI) antipsychotic drugs results in rapid D2 occupancy reductions. We explored if abrupt discontinuation of LAI …

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ESCRT Machinery Dysfunction in Motor Neurone Disease: TSG101, CHMP2B, and VPS4a Differentially Regulate TDP-43 Pathology, Autophagy, and Exosome Biogenesis

Laila Atef Mohamed, Mohamed Fouad Shalaby, Ritchie Williamson, Samantha Louise McLean et autres

Abstract Motor Neurone Disease (MND) is characterised by progressive degeneration of upper and lower motor neurons, accompanied by cytoplasmic mislocalisation and hyperphosphorylation of TDP-43 — hallmarks that implicate failure of endolysosomal proteostasis. The Endosomal Sorting Complexes Required for Transport (ESCRT) pathway governs …

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Distinct Endosomal Sorting Complexes Required for Transport Components Differentially Regulate Glutamate and Gamma-Aminobutyric Acid Receptor Surface Expression

Mohamed Fouad Shalaby, Samantha Louise McLean, Sriharsha Kantamneni

Abstract Endosomal sorting complexes required for transport (ESCRT) regulate membrane protein trafficking through coordinated cargo selection and endosomal processing, yet their contribution to neurotransmitter receptor sorting remains to be defined. Here, we examined how modulation of distinct complex components influences the surface …

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The Role of Dopamine Signaling and Neuroinflammation in Age‐Related Cognitive Dysfunction

Junior Bowen, Katie Hanna, Andrew M. J. Young, Gisela Helfer et autres

PURPOSE: Age-related cognitive decline is a growing public health concern, yet early molecular indicators remain poorly defined. Since brain changes often precede behavioral symptoms, identifying early markers of vulnerability is critical. Here, we investigated whether dopamine regulation and synaptic or inflammatory signaling …

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A stem cell secretome delays functional decline and supresses inflammation in two distinct models of neurodegeneration

S. Dickens, Andrew Parnell, Daniel Feist, Ben Mellows et autres

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with a rapidly increasing global prevalence. Current pharmacological interventions offer symptomatic relief but do not modify disease progression. Secretome-based therapeutics have emerged as a potential disease-modifying strategy, given their capacity to influence multiple …

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Author response for "The role of dopamine signalling and neuroinflammation in age-related cognitive dysfunction"

Junior Bowen, Katie Hanna, Andrew M. J. Young, Gisela Helfer et autres

Pharmacogenomics workshop: a mixed methods evaluation of trainee pharmacist knowledge and skill development, and workshop facilitator needs

Emma Groves, Jessica Keen, Samantha Louise McLean, Matthew E L Hardy et autres

OBJECTIVES: This study evaluated the impact of a pharmacogenomics (PGx) workshop on UK trainee pharmacists' knowledge, confidence, and application of PGx to simulated cases. The study also examined the experiences and support needs of workshop facilitators. METHODS: A mixed-methods design was employed, …

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Author response for "The role of dopamine signalling and neuroinflammation in age-related cognitive dysfunction"

Junior Bowen, Katie Hanna, Andrew M. J. Young, Gisela Helfer et autres

Correlations between receptor occupancy change and mental state in patients using long-acting injectable antipsychotics: MIDILIA pilot study

James Richard O’Neill, Chris J. L. Wilson, Mark Abie Horowitz, Samantha Louise McLean et autres

Background The rate at which psychosis drugs can be reduced in dose remains unclear. Anecdotal reports exist of people experiencing worsening of mental state before their next dose of long-acting injectable antipsychotic. No research has previously explored this phenomenon, but understanding this …

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EVALUATION OF PHYSICAL AND MOLECULAR PARAMETERS ON TRANSDUCTION IN CHIMERIC ANTIGEN RECEPTOR T-CELL (CAR-T) MANUFACTURING

Samantha Louise McLean, Pedro Silva Couto, Dale J. Stibbs, P. Springuel et autres

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Kainate Receptors Trafficking, Signalling and Functional Roles

Mahmoud F. Y. Shalaby, Vijay K. Pabbathi, Samantha Louise McLean, Sriharsha Kantamneni

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