Cullin-RING Ubiquitin Ligases in Neurodevelopment and Neurodevelopmental Disorders DOI Creative Commons

Honoka Ashitomi,

Tadashi Nakagawa,

Makiko Nakagawa

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 810 - 810

Published: March 28, 2025

Ubiquitination is a dynamic and tightly regulated post-translational modification essential for modulating protein stability, trafficking, function to preserve cellular homeostasis. This process orchestrated through hierarchical enzymatic cascade involving three key enzymes: the E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating E3 ubiquitin ligase. The final step of ubiquitination catalyzed by ligase, which facilitates transfer from enzyme substrate, thereby dictating proteins undergo ubiquitination. Emerging evidence underscores critical roles ligases in neurodevelopment, regulating fundamental processes such as neuronal polarization, axonal outgrowth, synaptogenesis, synaptic function. Mutations genes encoding consequent dysregulation these pathways have been increasingly implicated spectrum neurodevelopmental disorders, including autism disorder, intellectual disability, attention-deficit/hyperactivity disorder. review synthesizes current knowledge on molecular mechanisms underlying neurodevelopment Cullin-RING ligases—the largest subclass ligases—and their involvement pathophysiology disorders. A deeper understanding holds significant promise informing novel therapeutic strategies, ultimately advancing clinical outcomes individuals affected

Language: Английский

Cullin-RING Ubiquitin Ligases in Neurodevelopment and Neurodevelopmental Disorders DOI Creative Commons

Honoka Ashitomi,

Tadashi Nakagawa,

Makiko Nakagawa

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 810 - 810

Published: March 28, 2025

Ubiquitination is a dynamic and tightly regulated post-translational modification essential for modulating protein stability, trafficking, function to preserve cellular homeostasis. This process orchestrated through hierarchical enzymatic cascade involving three key enzymes: the E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating E3 ubiquitin ligase. The final step of ubiquitination catalyzed by ligase, which facilitates transfer from enzyme substrate, thereby dictating proteins undergo ubiquitination. Emerging evidence underscores critical roles ligases in neurodevelopment, regulating fundamental processes such as neuronal polarization, axonal outgrowth, synaptogenesis, synaptic function. Mutations genes encoding consequent dysregulation these pathways have been increasingly implicated spectrum neurodevelopmental disorders, including autism disorder, intellectual disability, attention-deficit/hyperactivity disorder. review synthesizes current knowledge on molecular mechanisms underlying neurodevelopment Cullin-RING ligases—the largest subclass ligases—and their involvement pathophysiology disorders. A deeper understanding holds significant promise informing novel therapeutic strategies, ultimately advancing clinical outcomes individuals affected

Language: Английский

Citations

0