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Synaptic plasticity is a central foundation of learning, memory, and cognitive function. Disruptions of synaptic processes are among the earliest events in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. While previous research has focused primarily on protein-coding genes, non-coding RNAs (ncRNAs) are increasingly recognized as important regulators of synaptic function. During previous funding periods, we systematically characterized the synaptic RNA repertoire (RNAome) in the brain and demonstrated that, in addition to mRNAs, numerous small non-coding RNAs are localized at synapses. Our work identified several microRNAs as well as small nucleolar RNAs (snoRNAs) that potentially regulate synaptic processes and are altered in neurodegenerative diseases.

In the new funding period, the project focuses on two key RNA classes:
(1) Synaptically localized microRNAs, particularly miR-370-3p, which can regulate neuronal activity, synaptic structure, and local protein synthesis and are altered in Alzheimer’s disease.
(2) Synaptic snoRNAs, especially SNORD115 and SNORD116, which may influence the organization of presynaptic structures through RNA-dependent protein condensates. By combining advanced molecular biology techniques, high-resolution imaging, and functional analyses of neuronal networks, we aim to investigate how these RNAs control synaptic plasticity and contribute to the pathology of neurodegenerative diseases.This project will elucidate fundamental mechanisms of RNA-based regulation of synaptic function and potentially identify novel targets for therapeutic strategies against neurodegenerative diseases.