Immunometabolic Basis of Neurodegenerative Disorders

Speaker: 

Dr. Mootaz M. Salman 

Department of Physiology, Anatomy and Genetics (DPAG), Kavli Institute for NanoScience Discovery, Medical Sciences Division, University of Oxford, Oxford, UK 

Biography of the speaker: 

Dr Mootaz Salman is a Group Leader in Cellular Neuroscience and an MRC Career Development Fellow in the Department of Physiology, Anatomy and Genetics (DPAG) at the University of Oxford. He is a Principal Investigator at the Oxford British Heart Foundation (BHF) Centre for Research Excellence and the UK Dementia Research Institute (UK DRI), with additional appointments at the Kavli Institute for Nanoscience Discovery. He is also a Governing Body Fellow and Research Fellow at Wolfson College, Oxford.  

Dr Salman moved to the University of Oxford in 2020, where he was awarded a Leverhulme Research Fellowship that enabled him to establish his independent research programme as a Departmental Research Lecturer. In 2022, he launched his research group at DPAG, which is primarily supported by his MRC Career Development Fellowship and further funded through competitive awards including a BBSRC Pioneer Award, CONNECT–Horizon 2020, ERC-related funding, a Chief Scientist Office Research Grant, and Royal Society support. He is also a named recipient of, and currently leads research under, the newly established BHF/UK DRI Principal Investigator Award.  

His research focuses on understanding the mechanisms of blood–brain barrier (BBB) dysfunction in neurodegenerative diseases and brain injury, with particular emphasis on endothelial metabolism, neuroimmune interactions, and vascular contributions to dementia. His group combines patient-derived stem cell technologies, genetic engineering, and advanced mechanobiological approaches to design and build innovative dynamic 3D multicellular human BBB and brain-on-a-chip models that accurately recapitulate human disease-relevant conditions, including neuroinflammation and vascular stress.  

Dr Salman is internationally recognised for his contributions to neuroscience and vascular biology. His accolades include the International Society of Neurochemistry (ISN) and APSN Young Neuroscientist Lectureship Award (2022), the Society for Experimental Biology President’s Medal for the Cell Biology Section (2024), the David Hague Early Career Investigator of the Year Award from Alzheimer’s Research UK (2024), and the inaugural ALBA–Roche Research Prize for Excellence in Neuroscience (2024). More recently, he was awarded the BAU Excellence Award for Medical Research and Innovation (2025) and the Geoffrey Burnstock Prize by the British Pharmacological Society.  

Description of the general focus of the symposium: 

Several neurodegenerative disorders (NDDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration (FTLD) share the hallmark feature of pathological protein aggregation despite their distincy clinical manifestations. Across these disorders, misfolded or aggregated proteins disrupt fundamental homeostatic pathways and trigger glial activation, ultimately driving progressive neuronal loss. Importantly,the impact of pathological protein aggregation in NDDs reflects cell- and context-specific vulnerabilities that are further shaped by systemic immunometabolic factors. Conditions, such as type 2 diabetes mellitus (DM2), obesity, and dyslipidemia are associated with increased risk and worse clinical course in AD and PD. In contrast, pre-clinical, as well as clinical studies in ALS consistently suggest protective effects of DM2, elevated body mass index (BMI), or dyslipidemia. These divergent observations underscore the overarching influence of systemic metabolic states and their differential effects on neurons and glia in determining NDD risk and progression. The blood–brain barrier (BBB) sits at the intersection of this systemic-central dialogue. Systemic metabolic alterations reshape endothelial metabolism, transporter function, cytokine responsiveness, and barrier permeability, enabling peripheral inflammatory cues to access neural tissue more readily. These shifts can impact microglial activation, astrocytic reactivity, and neuronal health, positioning BBB as an active participant rather than a passive barrier for NDDs risk and progression. This symposium brings these complementary perspectives to synthesize a unified immunometabolic framework for understanding NDDs. By examining how cellular metabolism, systemic metabolic states, and BBB function converge, the session will highlight shared mechanisms across NDDs. The session will further emphasise how insights from this integrated view can guide the development of therapeutic strategies aimed at boosting metabolic resilience, modulating neuroimmune interactions, or stabilising barrier integrity. 

From models to mechanisms: targeting BBB dysfunction in neurodegeneration 

Brief description of the talk: 

This presentation will explore how BBB dysfunction contributes to the etiology and progression of NDDs. It will outline the metabolic and structural determinants of BBB integrity, with emphasis on endothelial transport systems, tight-junction dynamics, and immune signaling pathways. Drawing on advanced experimental platforms, including 3D human BBB organoids, microfluidic systems, and high-resolution live imaging, the talk will illustrate how metabolic stress, inflammatory cues, and protein aggregates compromise BBB function. These mechanistic disruptions will be linked to downstream effects on glial activation, neuronal survival, and region-specific vulnerability. The talk will conclude with emerging therapeutic strategies aimed at stabilising or restoring BBB function, positioning the BBB as an active immunometabolic interface with a centralrole in neurodegenerative pathophysiology.