Neuroscience Ireland Conference 2025
Conference Speaker Profile
Prof. Gerard O’Keeffe
University College Cork,
Ireland
Talk Title
Disrupted Molecular Connectivity in Parkinson’s Disease: New Mechanisms and Therapeutic Targets
Talk Abstract
Parkinson’s disease (PD) is characterized by the progressive degeneration of midbrain dopaminergic neurons that project to the striatum via the nigrostriatal pathway. While dopaminergic neuron death is a pathological hallmark, increasing evidence suggests that earlier, potentially reversible impairments in molecular signalling and cellular communication contribute to disease progression. Our research investigates how disruptions in epigenetic regulation, neurotrophic support, and neuroimmune interactions lead to loss of connectivity and dopaminergic degeneration in PD.
Using in vivo models, primary neurons, and patient-derived samples, this talk will focus on Class IIa histone deacetylases (HDACs) as key molecular regulators of neuronal vulnerability in PD. We demonstrate that inhibition of Class IIa HDACs with the small molecule HDAC inhibitors (HDIs) confers neuroprotection in 6-hydroxydopamine (6-OHDA) PD models, preserving neurite architecture and motor function. Mechanistically, these HDIs upregulate the neurotrophic factor BMP2 and restores downstream signalling, which is necessary for its protective effects. In vivo, peripheral delivery of HDIs prevented 6-OHDA-induced dopaminergic neuron loss and suppressed microglial activation in the substantia nigra and striatum. These outcomes were accompanied by normalization of acetylated histone levels and HDAC5 distribution, underscoring the link between epigenetic modulation and cellular connectivity.
Together, these findings support a model in which disrupted epigenetic regulation drives impaired molecular communication in PD, and highlight targeted HDAC inhibition as a promising therapeutic approach to restore neuronal resilience and functional connectivity during early disease stages.
Speaker Biography
Professor Gerard O’Keeffe is Head of the Department of Anatomy and Neuroscience, and Vice-Head for Research and Innovation in the College of Medicine and Health at University College Cork. He brings over two decades of expertise in neuroscience, specializing in the molecular and cellular mechanisms driving Parkinson’s disease. His research employs a multidisciplinary approach integrating molecular neuroscience, epigenetics, transcriptomics, with in vivo disease models and patient samples to understand neuronal vulnerability and develop neuroprotective strategies.
Professor O’Keeffe earned his PhD from UCC and has held postdoctoral and visiting researcher roles at leading international institutions. His laboratory has made significant contributions to understanding the pathways underlying dopaminergic neuron degeneration and the potential for restoring neuronal connectivity through targeted interventions. His work has been recognized with prestigious awards including the Science Foundation Ireland Career Development Award and election as a Fellow of the Anatomical Society.
In addition to his research leadership, Professor O’Keeffe is deeply committed to fostering interdisciplinary collaboration, public engagement, and translating laboratory findings towards therapeutic development. He has played a key role in establishing research clusters and networks focused on neurodegeneration and continues to mentor the next generation of scientists within UCC and beyond.