Microtubules: A Key to Understand and Correct Neuronal Defects in CDKL5 Deficiency Disorder?

International Journal of Molecular Sciences

Roberta De Rosa¹  Charlotte Kilstrup-Nielsen¹  Isabella Barbiero¹ 

[1] Department of Biotechnology and Life Sciences, (DBSV), University of Insubria, Via Manara 7, 21052 Busto Arsizio (VA), Italy;

关键词: CDKL5;    microtubules;    neuronal morphology;    +TIP;    CLIP170;    EB1–3;    MAP1S;    microtubule-targeting agents;    pregnenolone;   

DOI  :  10.3390/ijms20174075

来源: DOAJ

【 摘 要 】

CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental encephalopathy caused by mutations in the X-linked CDKL5 gene that encodes a serine/threonine kinase. CDD is characterised by the early onset of seizures and impaired cognitive and motor skills. Loss of CDKL5 in vitro and in vivo affects neuronal morphology at early and late stages of maturation, suggesting a link between CDKL5 and the neuronal cytoskeleton. Recently, various microtubule (MT)-binding proteins have been identified as interactors of CDKL5, indicating that its roles converge on regulating MT functioning. MTs are dynamic structures that are important for neuronal morphology, migration and polarity. The delicate control of MT dynamics is fundamental for proper neuronal functions, as evidenced by the fact that aberrant MT dynamics are involved in various neurological disorders. In this review, we highlight the link between CDKL5 and MTs, discussing how CDKL5 deficiency may lead to deranged neuronal functions through aberrant MT dynamics. Finally, we discuss whether the regulation of MT dynamics through microtubule-targeting agents may represent a novel strategy for future pharmacological approaches in the CDD field.

【 授权许可】

Unknown