SEMINAR: Dual roles of microglia in Alzheimer's disease
Guest: Pinar Ayata, CUNY
Title: Dual roles of microglia in Alzheimer's disease (BIO)
Date/Time: 12 November 2025, 16:40
Location: Online, https://sabanciuniv.zoom.us/j/
Abstract: The brain’s primary immune cells, microglia, are a leading causal cell type in Alzheimer’s disease (AD). Yet, the mechanisms by which microglia can drive neurodegeneration remain unresolved. Here, we discover that a conserved stress signaling pathway, the integrated stress response (ISR), characterizes a microglia subset with neurodegenerative outcomes. Autonomous activation of ISR in microglia is sufficient to induce early features of the ultrastructurally distinct “dark microglia” linked to pathological synapse loss. In AD models, microglial ISR activation exacerbates neurodegenerative pathologies and synapse loss while its inhibition ameliorates them. Mechanistically, we present evidence that ISR activation promotes the secretion of toxic lipids by microglia, impairing neuron homeostasis and survival in vitro. Accordingly, pharmacological inhibition of ISR or lipid synthesis mitigates synapse loss in AD models. Our results demonstrate that microglial ISR activation represents a neurodegenerative phenotype, which may be sustained, at least in part, by the secretion of toxic lipids.
Bio: Pinar received her BSc in Biological and Biomedical Science in Turkey, where she was born and raised. During her undergraduate studies, she did summer internships at the German Cancer Research Center and Harvard Medical School. She embarked on her PhD thesis research in the lab of Dr. Nathaniel Heintz at The Rockefeller University. Here, she focused on understanding the interaction of 5-hydroxymethylcytosine modification and MeCP2 protein, and the pathophysiology of Rett syndrome. Pinar joined the lab of Dr. Anne Schaefer at Icahn School of Medicine at Mount Sinai for her post-doctoral work. There, she discovered brain regional heterogeneity of microglia and the epigenetic mechanisms that maintain this specification that are necessary for normal brain function. Pinar’s work has been published in prestigious journals, including Nature, Cell, Neuron, and Nature Neuroscience. She has received several awards, including the Women and Science Graduate Fellow Award, NARSAD Young Investigator Award, Robin Chemers Neustein Postdoctoral Award, Alzheimer's Association Grant, Kavli Foundation Scialog Award, and NIH R01 Research Project Grant.