Recombinant Mouse Tubulin beta-2A chain (Tubb2a)

What is the basic structure and function of Tubb2a in mouse models?

Tubb2a (beta-2A tubulin) is a crucial component of the cytoskeleton that exists as a heterodimer with alpha-tubulin to form microtubules. These microtubules provide structural support and facilitate intracellular transport within cells. Tubb2a plays significant roles in maintaining cell shape, enabling cell division, and facilitating organelle movement. The protein is particularly important in neuronal cells, where it contributes to neuronal migration, proliferation, and postmigrational development during cerebral cortex formation . Mouse Tubb2a shares high sequence homology with human TUBB2A, making it a valuable model for studying tubulin-related pathologies.

How does Tubb2a differ from other beta-tubulin isoforms in mouse models?

While mouse Tubb2a shares significant sequence homology with other beta-tubulin isoforms, particularly Tubb2b (approximately 99% amino acid sequence homology), it has distinct expression patterns and functional significance. The presence of multiple beta-tubulin isoforms allows for functional diversity and adaptive responses to cellular needs. The T7 loop region, which contains critical residues including positions 247 and 248, is particularly important for GTP binding and interaction with alpha-tubulin . Specific amino acid differences in this region and others contribute to the unique properties of Tubb2a compared to other beta-tubulin isoforms, influencing microtubule dynamics, stability, and interactions with microtubule-associated proteins.

What is known about the expression patterns of Tubb2a in mouse developmental stages?

Tubb2a is highly expressed in developing mouse brain tissue, alongside other neuronal beta-tubulin isoforms including Tubb2b, Tubb3, and Tubb. Its expression is particularly important during the three major overlapping events of mammalian cerebral cortex development: cell proliferation, neuronal migration, and postmigrational development . Studies examining mouse models with Tubb2a mutations, such as the p.Asn247Ser substitution identified in the brdp mouse model, have demonstrated the critical role of this tubulin isoform in cortical development . The temporal and spatial expression patterns of Tubb2a during mouse development are tightly regulated, with expression levels changing throughout neurodevelopment.

What are the recommended methods for detecting mouse Tubb2a in experimental samples?

Multiple techniques can be employed to detect mouse Tubb2a in experimental samples:

When detecting mouse Tubb2a, using specific antibodies is crucial due to the high sequence homology with other beta-tubulin isoforms. Verification of antibody specificity through appropriate controls is essential for accurate detection .

How should researchers design microtubule incorporation assays for recombinant Tubb2a?

To effectively design microtubule incorporation assays for recombinant Tubb2a:

• Expression system: Transfect human embryonic kidney 293 (HEK293) cells with wild-type or variant Tubb2a expression constructs to analyze incorporation into the cellular microtubule network .

• Visualization: Use immunofluorescence with specific antibodies against tagged Tubb2a to visualize its incorporation into microtubules.

• Cold-induced depolymerization: To assess dynamic properties, subject cells to cold treatment (4°C) to induce microtubule depolymerization, then return to 37°C to observe repolymerization rates .

• Quantification methods:

  • Measure the proportion of Tubb2a protein that remains unpolymerized in the cytoplasm versus incorporation into defined microtubule structures

  • Assess the rate of reincorporation into growing microtubules following cold-induced depolymerization

  • Compare polymerization and depolymerization rates between wild-type and variant Tubb2a proteins

These assays can be particularly valuable for functional characterization of Tubb2a variants and their effects on microtubule dynamics.

What experimental approaches are optimal for studying Tubb2a GTP binding and hydrolysis?

GTP binding and hydrolysis are critical for tubulin function. To study these processes in Tubb2a:

• In vitro GTP binding assays:

  • Use radiolabeled GTP analogs to measure binding kinetics

  • Employ fluorescent GTP analogs with fluorescence polarization to assess binding affinities

  • Apply isothermal titration calorimetry to determine thermodynamic parameters of GTP binding

• GTPase activity measurements:

  • Utilize colorimetric phosphate release assays to quantify GTP hydrolysis rates

  • Implement HPLC-based methods to measure GTP/GDP ratios

  • Use real-time fluorescence-based assays with specialized GTP analogs

• Structural analysis:

  • Apply in silico modeling to predict how specific residues affect GTP interactions at the intradimer interface between alpha- and beta-tubulin subunits

  • Focus on the T7 loop region, which has been implicated in GTP binding based on studies of Asn247 and Ala248 residues

• Mutational analysis:

  • Generate specific mutations in residues predicted to affect GTP binding, such as those in the T7 loop

  • Compare GTP binding and hydrolysis parameters between wild-type and mutant proteins

These approaches can provide valuable insights into how Tubb2a variants affect GTP interactions and subsequent microtubule dynamics.

How can mouse Tubb2a be used to model human TUBB2A-related tubulinopathies?

Mouse Tubb2a can serve as an effective model for human TUBB2A-related tubulinopathies due to high sequence conservation and functional similarity. Researchers should consider the following methodological approaches:

• Generation of transgenic mouse models:

  • Introduce specific mutations corresponding to human pathogenic variants (e.g., p.Asn247Lys, p.Ala248Val, p.Gly98Arg) using CRISPR-Cas9 gene editing

  • Create conditional knockout models to study the temporal and spatial requirements for Tubb2a during development

  • Develop knock-in models that express fluorescently tagged Tubb2a to visualize dynamics in vivo

• Phenotypic characterization:

  • Perform comprehensive neuroanatomical assessment, focusing on cortical development, corpus callosum formation, and basal ganglia structure

  • Evaluate for specific brain malformations seen in human patients, such as pachygyria, corpus callosum abnormalities, and hypoplasia of brain structures

  • Conduct behavioral testing for features corresponding to human symptoms like intellectual disability, seizures, and autism spectrum disorder

• Cellular and molecular analysis:

  • Examine neuronal migration, proliferation, and differentiation during development

  • Assess microtubule dynamics and organization in primary neuronal cultures

  • Evaluate axonal transport and neuronal connectivity

• Comparative studies:

  • Directly compare phenotypes of mouse models with clinical findings in human patients

  • Analyze differences in phenotypic severity between variants affecting different functional domains of the protein

This methodological framework enables researchers to investigate pathogenic mechanisms and potential therapeutic approaches for TUBB2A-related disorders.

What approaches should be used to investigate the role of Tubb2a in neuronal migration and cortical development?

To investigate Tubb2a's role in neuronal migration and cortical development:

• In utero electroporation:

  • Introduce wild-type or mutant Tubb2a constructs into developing mouse cortex at specific embryonic stages

  • Track neuronal migration using fluorescently tagged constructs

  • Analyze effects on cortical layering and neuronal positioning

• Ex vivo brain slice cultures:

  • Culture embryonic brain slices containing fluorescently labeled neurons

  • Perform time-lapse imaging to track migration in real-time

  • Test effects of Tubb2a mutants or knockdown on migration velocity and trajectory

• Cellular assays:

  • Examine microtubule dynamics in migrating neurons using live imaging

  • Analyze leading process formation and nucleokinesis in primary neuronal cultures

  • Investigate interactions between Tubb2a and migration-related proteins

• Molecular analysis of signaling pathways:

  • Evaluate how Tubb2a variants affect signaling pathways critical for migration

  • Assess interactions with cytoskeletal regulators and molecular motors

  • Perform comparative phosphoproteomics to identify altered signaling networks

• Analysis of neuronal positioning:

  • Assess cortical layer formation through immunohistochemistry for layer-specific markers

  • Evaluate the distribution of specific neuronal subtypes

  • Analyze the formation of cortical gyri and sulci in relation to Tubb2a function

These methodological approaches can reveal how Tubb2a contributes to neuronal migration and cortical development, and how mutations lead to cortical malformations observed in tubulinopathies.

How can researchers effectively design structure-function studies for Tubb2a variants?

Designing effective structure-function studies for Tubb2a variants requires a multifaceted approach:

• In silico structural analysis:

  • Use homology modeling and molecular dynamics simulations to predict structural consequences of variants

  • Focus on critical regions like the T7 loop, which contains residues important for GTP binding and alpha/beta-tubulin heterodimer formation

  • Predict effects on protein folding, heterodimer stability, and polymerization potential

• Site-directed mutagenesis:

  • Generate recombinant constructs with specific variants of interest

  • Create mutations in different functional domains to understand domain-specific effects

  • Include both naturally occurring pathogenic variants (e.g., p.Asn247Lys, p.Ala248Val) and designed variants to test structural hypotheses

• Heterodimer formation and polymerization assays:

  • Assess the ability of variant Tubb2a to form heterodimers with alpha-tubulin

  • Evaluate incorporation into growing microtubule polymers in cellular systems

  • Quantify the proportion of variant protein that remains unpolymerized versus incorporated into the cytoskeleton

• Dynamic property assessment:

  • Measure polymerization and depolymerization rates of microtubules containing variant Tubb2a

  • Assess microtubule stability under various conditions (temperature, drug treatments)

  • Evaluate post-translational modification patterns on variant tubulins

• Interaction studies:

  • Identify altered interactions with microtubule-associated proteins

  • Assess binding to molecular motors and other transport machinery

  • Evaluate effects on GTP binding and hydrolysis

This integrated approach allows researchers to connect structural alterations to functional consequences and provide insights into pathogenic mechanisms of Tubb2a variants.

How should researchers interpret functional data from different Tubb2a variants in experimental models?

Interpreting functional data from Tubb2a variants requires careful consideration of multiple factors:

• Systematic classification of functional defects:

• Correlation with structural predictions:

  • Assess whether experimental data aligns with in silico predictions

  • Consider the structural location of the variant (e.g., T7 loop variants like p.Asn247Lys and p.Ala248Val affect GTP interactions)

  • Evaluate whether the variant affects conserved or variable regions of the protein

• Phenotypic spectrum analysis:

  • Compare the severity of functional defects with clinical phenotypes

  • Assess whether phenotypic variability correlates with differences in functional impairment

  • Consider that some variants (e.g., p.Ala248Val) may cause subtle functional effects while still resulting in clinical phenotypes

• Consideration of genetic context:

  • Evaluate the effects of variants in different genetic backgrounds

  • Consider potential modifier genes that may influence phenotypic expression

  • Assess species-specific differences when translating between mouse and human studies

• Integration of multiple assays:

  • No single assay fully captures tubulin functionality

  • Combine data from cellular, biochemical, and structural approaches

  • Consider that some variants may affect specific functions while sparing others

This comprehensive approach to data interpretation can help researchers understand the complex relationships between Tubb2a variants, functional defects, and resulting phenotypes.

What methodologies are recommended for resolving conflicting data about Tubb2a variant pathogenicity?

When facing conflicting data about Tubb2a variant pathogenicity, researchers should implement these methodological approaches:

• Standardize experimental conditions:

  • Use consistent expression systems and cellular models

  • Standardize protein purification methods and buffer conditions

  • Employ identical assay protocols across variant studies

• Perform comparative analysis across multiple functional assays:

  • Assess variants using multiple complementary techniques

  • Compare results from in vitro biochemical assays with cellular studies

  • Evaluate both static and dynamic properties of tubulin function

• Utilize the American College of Medical Genetics and Genomics (ACMG) framework:

  • Apply systematic variant classification criteria including:

    • Population frequency data (e.g., absence from population databases like Genome Aggregation Database)

    • Computational predictions (e.g., PROVEAN, CADD, MutTaster, REVEL scores)

    • Functional studies

    • Segregation with disease in families

    • Occurrence as de novo variants in multiple unrelated individuals

• Implement quantitative measures of pathogenicity:

  • Develop scoring systems that integrate multiple lines of evidence

  • Use statistical approaches to weigh evidence from different sources

  • Apply Bayesian frameworks to calculate probabilities of pathogenicity

• Consider variant-specific contexts:

  • Evaluate whether conflicting results might be explained by genetic background differences

  • Assess whether experimental conditions might differentially affect specific variants

  • Consider whether distinct cellular contexts might reveal different aspects of pathogenicity

• Cross-reference with homologous proteins:

  • Examine whether equivalent variants in highly homologous proteins (e.g., TUBB2B) show similar effects

  • The p.Ala248Val variant in TUBB2A has an identical counterpart in TUBB2B associated with polymicrogyric cortical malformations

By systematically applying these approaches, researchers can resolve conflicting data and establish more reliable determinations of variant pathogenicity.

How can researchers design experiments to determine the mechanistic impact of specific Tubb2a mutations on GTP binding?

To determine the mechanistic impact of Tubb2a mutations on GTP binding:

• Structure-guided mutation selection:

  • Focus on residues in or near the GTP-binding pocket and intradimer interface

  • Pay special attention to the T7 loop region, which contains critical residues (e.g., positions 247-248) implicated in GTP interactions

  • Include variants with predicted direct and indirect effects on GTP binding

• Direct GTP binding measurements:

  • Implement fluorescence-based GTP binding assays using fluorescent GTP analogs

  • Utilize isothermal titration calorimetry to determine binding affinities and thermodynamic parameters

  • Apply surface plasmon resonance to measure binding kinetics

  • Compare binding parameters between wild-type and mutant proteins under identical conditions

• Structural analysis approaches:

  • Perform X-ray crystallography or cryo-electron microscopy of wild-type and mutant proteins

  • Use hydrogen-deuterium exchange mass spectrometry to detect conformational changes affecting the GTP binding region

  • Apply molecular dynamics simulations to model dynamic aspects of GTP interactions

• Functional consequences assessment:

  • Analyze how altered GTP binding affects heterodimer formation with alpha-tubulin

  • Evaluate impacts on microtubule polymerization and dynamic instability

  • Measure GTPase activity to determine if mutations affect not only binding but also hydrolysis

• Comparative studies with established variants:

  • Include known GTP-binding affecting variants like p.Asn247Lys as positive controls

  • Use variants known to affect tubulin function through other mechanisms as specificity controls

  • Compare results with equivalent mutations in other beta-tubulin isoforms

• Integrated data analysis:

  • Correlate structural changes with functional outcomes

  • Develop models explaining how specific residue changes alter the GTP binding pocket

  • Generate testable hypotheses about the mechanisms underlying pathogenicity

This systematic experimental approach can elucidate how specific Tubb2a mutations affect GTP binding and contribute to disease mechanisms in tubulinopathies.

What are the major technical challenges when working with recombinant mouse Tubb2a, and how can they be addressed?

Working with recombinant mouse Tubb2a presents several technical challenges:

• Protein solubility and stability issues:

  • Challenge: Tubulin proteins often aggregate when expressed recombinantly.

  • Solution: Optimize expression conditions including temperature (lower temperatures often improve folding), use solubility tags (e.g., SUMO, MBP), and include molecular chaperones during expression. Consider using insect cell or mammalian expression systems rather than bacterial systems.

• Heterodimer formation requirements:

  • Challenge: Beta-tubulin requires alpha-tubulin for proper folding and function.

  • Solution: Co-express alpha- and beta-tubulin, or use in vitro reconstitution systems with purified native alpha-tubulin. Consider expressing pre-formed alpha/beta dimers rather than individual subunits.

• Post-translational modification complexity:

  • Challenge: Native tubulin undergoes numerous post-translational modifications crucial for function.

  • Solution: Use mammalian or insect cell expression systems that can perform relevant modifications. Alternatively, perform in vitro modifications using purified modifying enzymes for specific studies.

• Distinguishing from endogenous tubulin:

  • Challenge: High homology between tubulin isoforms complicates specific detection.

  • Solution: Use epitope tags that don't interfere with function, or develop highly specific antibodies against unique Tubb2a regions. Implement CRISPR-edited cell lines where endogenous tubulin is replaced with tagged versions.

• Maintaining native-like properties:

  • Challenge: Ensuring recombinant protein behaves like native protein.

  • Solution: Validate recombinant protein through comparative functional assays with native tubulin. Assess polymerization properties, GTP binding, and interactions with microtubule-associated proteins.

• Analyzing dynamic behaviors:

  • Challenge: Capturing the dynamic nature of microtubules in experimental systems.

  • Solution: Implement live-cell imaging approaches with fluorescently tagged tubulins. Use total internal reflection fluorescence (TIRF) microscopy for in vitro dynamic assays.

These methodological approaches can help researchers overcome the technical challenges associated with recombinant Tubb2a studies.

How can researchers better understand the tissue-specific effects of Tubb2a mutations?

To better understand tissue-specific effects of Tubb2a mutations:

• Develop tissue-specific expression models:

  • Generate conditional knock-in mouse models with Cre-lox systems to express Tubb2a mutations in specific tissues or cell types

  • Use tissue-specific promoters to drive expression of mutant Tubb2a in specific regions

  • Implement organoid models derived from different tissues to study context-dependent effects

• Comparative expression profiling:

  • Perform RNA-seq analysis across different tissues to determine natural expression patterns of Tubb2a

  • Identify tissue-specific co-expression networks that might influence Tubb2a function

  • Map expression patterns of other tubulin isoforms to identify potential compensatory mechanisms

• Interactome analysis:

  • Use proximity labeling techniques (BioID, APEX) to identify tissue-specific Tubb2a interacting partners

  • Perform comparative proteomics across different cell types expressing the same Tubb2a variant

  • Identify tissue-specific post-translational modifications that might affect mutant protein function

• Single-cell approaches:

  • Apply single-cell RNA-seq to identify cell populations particularly vulnerable to Tubb2a mutations

  • Use single-cell protein analysis to detect heterogeneous responses to Tubb2a dysfunction

  • Implement lineage tracing to follow the fate of cells expressing mutant Tubb2a during development

• Functional consequence assessment:

  • Compare cellular phenotypes across different tissue types expressing the same mutation

  • Analyze tissue-specific microtubule organization and dynamics in response to mutations

  • Evaluate whether specific cellular processes (e.g., migration, division, transport) are differentially affected

This comprehensive approach can reveal why certain tissues, particularly the developing brain, are especially vulnerable to Tubb2a mutations and help explain the predominantly neurological phenotypes observed in tubulinopathies .

What emerging technologies hold promise for advancing Tubb2a functional studies?

Several emerging technologies show significant promise for advancing Tubb2a functional studies:

• Advanced imaging technologies:

  • Super-resolution microscopy techniques (STORM, PALM, SIM) for visualizing microtubule structures beyond the diffraction limit

  • Lattice light-sheet microscopy for long-term, low-phototoxicity imaging of microtubule dynamics in living cells

  • Cryo-electron tomography to visualize native microtubule structures and associated proteins in cellular contexts

• Genome editing and screening approaches:

  • CRISPR base editing and prime editing for precise introduction of specific Tubb2a variants

  • CRISPR screening libraries targeting Tubb2a interactors to identify genetic modifiers

  • CRISPR-engineered reporter cell lines for high-throughput variant analysis

• Protein engineering and synthetic biology:

  • Engineered tubulin molecules with built-in sensors for GTP binding, conformation changes, or protein interactions

  • Optogenetic tools to control Tubb2a activity or interactions with temporal and spatial precision

  • Synthetic microtubule systems with defined components for mechanistic studies

• Systems biology approaches:

  • Multi-omics integration combining transcriptomics, proteomics, and metabolomics data

  • Network analysis to understand Tubb2a within the broader cytoskeletal regulation context

  • Computational modeling of microtubule dynamics incorporating Tubb2a variants

• Organoid and microphysiological systems:

  • Brain organoids to model cortical development with Tubb2a mutations in a human context

  • Organ-on-chip systems to study Tubb2a function in complex tissue environments

  • Patient-derived induced pluripotent stem cells differentiated into relevant cell types

• AI and machine learning applications:

  • Deep learning analysis of microtubule dynamics from time-lapse microscopy

  • Predictive modeling of variant effects based on protein structure and evolutionary conservation

  • Automated phenotypic classification of cellular responses to Tubb2a variants

These emerging technologies offer unprecedented opportunities to understand Tubb2a function at multiple scales, from molecular interactions to organismal phenotypes, potentially leading to new therapeutic strategies for tubulinopathies.

How do findings from mouse Tubb2a studies translate to human TUBB2A-related disorders?

Findings from mouse Tubb2a studies have significant translational relevance to human TUBB2A-related disorders, though with important considerations:

• Conserved molecular mechanisms:

  • The high sequence homology (>98%) between mouse Tubb2a and human TUBB2A enables direct comparison of molecular mechanisms

  • Studies of specific variants like p.Asn247Lys and p.Ala248Val in mouse models have revealed mechanisms potentially applicable to human patients

  • Effects on GTP binding, heterodimer formation, and microtubule incorporation observed in mouse models likely reflect similar processes in humans

• Phenotypic correlations:

  • Mouse models with Tubb2a mutations show brain malformations similar to those in human tubulinopathies, including cortical dysplasia and corpus callosum abnormalities

  • Both mice and humans with TUBB2A mutations exhibit neurological symptoms including developmental delay and seizures

  • The identification of hypoplastic right caudate nucleus and signal abnormality in the periaqueductal gray matter in human patients may guide focused examination of these structures in mouse models

• Translational limitations:

  • Mouse cortical development differs from human in complexity and timeline

  • Some features of human tubulinopathies, such as specific patterns of polymicrogyria, may be difficult to model precisely in mice

  • The spectrum of behavioral phenotypes, including autism spectrum disorder reported in some human patients, requires careful translational assessment

• Therapeutic implications:

  • Mouse models provide platforms for testing potential therapeutic approaches

  • Understanding shared mechanisms between mouse and human tubulinopathies may reveal targetable pathways

  • Mouse studies can identify critical developmental windows for potential intervention

The translational value of mouse Tubb2a research is enhanced when combined with studies using human cellular models, such as induced pluripotent stem cells and brain organoids, providing complementary insights into TUBB2A-related disorders.

What are the most significant unresolved questions in Tubb2a research?

Several significant unresolved questions remain in Tubb2a research:

• Isoform-specific functions:

  • Why do mutations in different tubulin isoforms, despite high sequence homology, lead to distinct phenotypic outcomes?

  • What are the unique functional properties of Tubb2a compared to other beta-tubulin isoforms?

  • How do cells regulate the incorporation of different tubulin isoforms into specific microtubule populations?

• Phenotypic variability mechanisms:

  • What accounts for the variable expressivity observed in patients with identical TUBB2A mutations?

  • What genetic, epigenetic, or environmental factors modify the phenotypic expression of Tubb2a mutations?

  • How do stochastic developmental events influence the final phenotypic outcome of Tubb2a mutations?

• Developmental timing effects:

  • At what developmental stages is Tubb2a function most critical?

  • Are there temporal windows during which Tubb2a dysfunction causes specific malformations?

  • How does the developmental regulation of Tubb2a expression influence phenotypic outcomes?

• Cell type-specific vulnerabilities:

  • Why are certain neuronal populations particularly vulnerable to Tubb2a dysfunction?

  • What cellular processes are most sensitive to alterations in Tubb2a function?

  • How do different cell types cope with or compensate for Tubb2a mutations?

• Therapeutic potential:

  • Can tubulin dysfunction be targeted therapeutically, particularly after development?

  • Are there approaches to enhance compensation by other tubulin isoforms?

  • Could modulation of microtubule dynamics ameliorate symptoms in established tubulinopathies?

• Structure-function relationships:

  • How do specific amino acid changes in Tubb2a translate to altered microtubule properties?

  • What is the precise structural mechanism by which T7 loop mutations affect GTP binding and heterodimer formation?

  • How do post-translational modifications influence the function of wild-type versus mutant Tubb2a?

Addressing these questions will require interdisciplinary approaches combining structural biology, developmental neuroscience, genetics, and clinical research.

How might understanding Tubb2a function contribute to therapeutic approaches for tubulinopathies?

Understanding Tubb2a function could contribute to therapeutic approaches for tubulinopathies through several potential pathways:

• Targeted stabilization of heterodimer formation:

  • For mutations affecting heterodimer stability, small molecules could be developed to stabilize the alpha/beta-tubulin interface

  • Chemical chaperones might promote proper folding of mutant tubulins with mild structural defects

  • Enhancing intracellular chaperone function could improve the processing of mildly defective Tubb2a proteins

• Modulation of microtubule dynamics:

  • Fine-tuned application of microtubule-stabilizing or destabilizing agents might compensate for altered dynamics caused by Tubb2a mutations

  • Development of isoform-specific modulators could target affected microtubule populations while sparing others

  • Temporal control of treatment could allow intervention during critical developmental periods

• Gene therapy approaches:

  • Antisense oligonucleotides could be used to selectively reduce expression of mutant alleles

  • CRISPR-based approaches might correct specific mutations in affected tissues

  • Viral vector-mediated delivery of wild-type Tubb2a could supplement defective protein function

• Compensation through other tubulin isoforms:

  • Upregulation of compensatory tubulin isoforms might mitigate Tubb2a dysfunction

  • Understanding the regulation of tubulin gene expression could reveal targets for modulating isoform balance

  • Identification of shared functions across isoforms could guide compensatory approaches

• Targeting downstream pathways:

  • Identification of disrupted signaling pathways secondary to Tubb2a dysfunction could reveal therapeutic targets

  • Neuroprotective approaches might prevent secondary neuronal damage in tubulinopathies

  • Anti-epileptic strategies tailored to tubulinopathy mechanisms could improve seizure control

• Cellular replacement strategies:

  • Neural stem cell transplantation might partially restore function in affected brain regions

  • Correction of Tubb2a mutations in patient-derived cells followed by transplantation could provide functional cells