Nataliya Kolotyeva

Abstract: Metabolic plasticity fundamentally regulates the sleep-wake cycle, with lactate serving as both a key energy substrate and signaling molecule. Cerebral lactate rises during wakefulness and REM sleep but declines in NREM sleep. Recent evidence links impaired NAD+ metabolism to Parkinson's disease, where reduced levels in dopaminergic neurons compromise ATP production. Pro-inflammatory signals trigger Warburg-like glycolysis, elevating lactate. Beyond energy metabolism, lactate regulates gene expression, Ca²⁺ signaling, cell differentiation, and myelination. Astrocytes are the primary lactate producers, supporting neurons via monocarboxylate transporters and the lactate receptor GPR81, whose CNS functions remain incompletely understood. In Alzheimer's and Parkinson's diseases, chronic disruption of lactate metabolism impairs astrocyte-neuron coupling, causing synaptic energy deficits and hindering sleep-dependent memory consolidation. Abnormal lactate dynamics also mark glymphatic dysfunction: sleep loss reduces clearance of lactate, β-amyloid, and tau, fostering neuroinflammation and cognitive decline. Clinically, lactate holds promise as a biomarker for early detection of sleep-related disorders. Non-invasive magnetic resonance spectroscopy enables real-time metabolite monitoring. Therapeutic strategies targeting sleep normalization, lactate metabolism modulation, and GPR81 signaling may optimize glymphatic clearance and mitigate neurodegeneration, paving the way for personalized interventions in sleep-associated cognitive disorders.

Speaker: Nataliya Kolotyeva, Doctor of Medical Sciences, Associate Professor. Head of the Laboratory of Experimental and Translational Neurochemistry at the Brain Institute of the Russian Center of Neurology and Neurosciences; Professor of the Chair of Biological Chemistry at the Russian University of Medicine; Professor of the Chair of Biomedical Technical Systems at the Bauman Moscow State Technical University. Her research interests focus on studying the cellular and molecular mechanisms of metabolic plasticity in the neurovascular unit in age-related neurodegenerative diseases, modeling neurodegeneration and neuroinflammation using primary brain cell cultures, as well as on investigating the role of redox homeostasis imbalance, aberrant lactate and NAD⁺ metabolism in the pathogenesis of Alzheimer’s and Parkinson’s diseases. The research focuses particularly on developing optimized methods for the early diagnosis of neurodegenerative diseases based on the detection of proteins with aberrant conformation and on creating digital twins of cellular systems for microfluidic platforms.
She is the author and co-author of articles in peer-reviewed international journals in the fields of neurochemistry, molecular medicine, and biomedical technologies. She lectures and conducts practical sessions on biochemistry, molecular medicine, and regenerative medicine, serving as a research advisor to graduate students.
As a leader and executor, she participates in scientific projects aimed at studying the mechanisms of neurodegeneration, developing innovative diagnostic approaches, and implementing interdisciplinary solutions at the intersection of neuroscience, biochemistry, and engineering.