Tubulinopathies are a group of recently described diseases characterized by mutations in the tubulin genes. Mutations in TUBB4A produce diseases such as dystonia type 4 (DYT4) and hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC), which are clinically diagnosed by magnetic resonance imaging (MRI). We propose the taiep rat as the first animal model for tubulinopathies. The spontaneous mutant suffers from a syndrome related to a central leukodystrophy and characterized by tremor, ataxia, immobility, epilepsy, and paralysis. The pathological signs presented by these rats and the morphological changes we found by our longitudinal MRI study are similar to those of patients with mutations in TUBB4A. The diffuse atrophy we found in brain, cerebellum and spinal cord is related to the changes detectable in many human tubulinopathies and in particular in H-ABC patients, where myelin degeneration at the level of putamen and cerebellum is a clinical trademark of the disease. We performed Tubb4a exon analysis to corroborate the genetic defect and formulated hypotheses about the effect of amino acid 302 change on protein physiology. Optical microscopy of taiep rat cerebella and spinal cord confirmed the optical density loss in white matter associated with myelin loss, despite the persistence of neural fibers.

Hypomyelination with atrophy of the basal ganglia and cerebellum (H‐ABC) is a neurodegenerative disease due to mutations in TUBB4A. Patients suffer from extrapyramidal movements, spasticity, ataxia, and cognitive deficits. Magnetic resonance imaging features are hypomyelination and atrophy of the striatum and cerebellum. A correlation between the mutations and their cellular, tissue and organic effects is largely missing. The effects of these mutations on sensory functions have not been described so far. We have previously reported a rat carrying a TUBB4A (A302T) mutation and sharing most of the clinical and radiological signs with H‐ABC patients. Here, for the first time, we did a comparative study of the hearing function in an H‐ABC patient and in this mutant model. By analyzing hearing function, we found that there are no significant differences in the auditory brainstem response (ABR) thresholds between mutant rats and WT controls. Nevertheless, ABRs show longer latencies in central waves (II–IV) that in some cases disappear when compared to WT. The patient also shows abnormal AEPs presenting only Waves I and II. Distortion product of otoacoustic emissions and immunohistochemistry in the rat show that the peripheral hearing function and morphology of the organ of Corti are normal. We conclude that the tubulin mutation severely impairs the central hearing pathway most probably by progressive central white matter degeneration. Hearing function might be affected in a significant fraction of patients with H‐ABC; therefore, screening for auditory function should be done on patients with tubulinopathies to evaluate hearing support therapies.

Carbon dots (CDs) are carbon nanoparticles with sizes below 10 nm and have attracted attention due to their relatively low toxicity, great biocompatibility, water solubility, facile synthesis, and exceptional photoluminescence properties. Accordingly, CDs have been widely exploited in different sensing and biomedical applications, for example, metal sensing, catalysis, biosensing, bioimaging, drug and gene delivery, and theragnostic applications. Similarly, the well-known properties of silica, such as facile surface functionalization, good biocompatibility, high surface area, and tunable pore volume, have allowed the loading of diverse inorganic and organic moieties and nanoparticles, creating complex hybrid nanostructures that exploit distinct properties (optical, magnetic, metallic, mesoporous, etc.) for sensing, biosensing, bioimaging, diagnosis, and gene and drug delivery. In this context, CDs have been successfully grafted into diverse silica nanostructures through various synthesis methods (e.g., solgel chemistry, inverse microemulsion, surfactant templating, and molecular imprinting technology (MIT)), imparting hybrid nanostructures with multimodal properties for distinct objectives. This review discusses the recently employed synthesis methods for CDs and silica nanoparticles and their typical applications. Then, we focus on combined synthesis techniques of CD–silica nanostructures and their promising biosensing operations. Finally, we overview the most recent potential applications of these materials as innovative smart hybrid nanocarriers and theragnostic agents for the nanomedical field. Graphical abstract

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The cover image is based on the Research Article Auditory impairment in H‐ABC tubulinopathy by Alejandra Lopez‐Juarez et al., https://doi.org/10.1002/cne.24990.