Centrosomes and cilia in neurodegeneration: main actors or mere spectators?

: Centrosomes are intracellular organelles traditionally recognized as the primary microtubule (MT) organizing centres (MTOCs) in the cell, playing a crucial role in organizing the cytoskeleton and forming the MT-based spindle during cell division. However, it is now well established that centrosomes also function as central hubs for a wide range of signalling pathways. In non-dividing cells, they give rise to the primary cilium, a surface antenna that serves as a key structure for signalling. Neurons are highly specialized cells with a distinctive morphology, and most neurons have cilia. During brain development, cilia regulate the self-renewal of neural progenitors, as well as the differentiation, migration and synapse formation of newly generated neurons. As a consequence, defects in cilia result in various neurodevelopmental disorders. The role of centrosomes and cilia in neurodegeneration, or the progressive loss of neurons, is less understood. Centrosomes take part in several cellular processes that are often disrupted in neurodegenerative diseases (NDDs), and many proteins associated with these conditions have been found at centrosomes or cilia suggesting a link between these organelles and the underlying mechanisms that contribute to neuronal decline. Unravelling if and how centrosome dysfunction contributes to neurodegeneration could significantly deepen our understanding of the underlying biology of these disorders. Such insights may pave the way for new therapeutic approaches to address these debilitating conditions.