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Synthetic excitatory synaptic organizer The human brain contains trillions of synapses within a vast network of neurons. Synapse remodeling is essential to ensure the efficient reception and integration of external stimuli and to store and retrieve information. Building and remodeling of synapses occurs throughout life under the control of synaptic organizer proteins. Errors in this process can lead to neuropsychiatric or neurological disorders. Suzuki et al. combined structural elements of natural synaptic organizers to develop an artificial version called CPTX, which has different binding properties (see the Perspective by Salinas). CPTX could act as a molecular bridge to reconnect neurons and restore excitatory synaptic function in animal models of cerebellar ataxia, familial Alzheimer's disease, and spinal cord injury. The findings illustrate how structure-guided approaches can help to repair neuronal circuits. Science , this issue p. eabb4853 ; see also p. 1052

Autosomal-recessive cerebellar ataxias (ARCAs) comprise a heterogeneous group of rare degenerative and metabolic genetic diseases that share the hallmark of progressive damage of the cerebellum and its associated tracts. This Review focuses on recent translational research in ARCAs and illustrates the steps from genetic characterization to preclinical and clinical trials. The emerging common pathways underlying ARCAs include three main clusters: mitochondrial dysfunction, impaired DNA repair, and complex lipid homeostasis. Novel ARCA treatments might target common hubs in pathogenesis by modulation of gene expression, stem cell transplantation, viral gene transfer, or interventions in faulty pathways. All these translational steps are addressed in current ARCA research, leading to the expectation that novel treatments for ARCAs will be reached in the next decade.