Gigaxonin (GAN) (GAN)

Gigaxonin is a protein encoded by the GAN gene that functions as a substrate adaptor for the Cullin-3 E3 ubiquitin ligase complex. It plays a vital role in maintaining the neuronal cytoskeleton by facilitating the ubiquitination and subsequent proteasomal degradation of intermediate filaments, such as neurofilaments and vimentin (UniProt Consortium, 2023). Mutations in the GAN gene lead to Giant Axonal Neuropathy (GAN), a rare and fatal autosomal recessive neurodegenerative disorder characterized by the toxic accumulation of neurofilaments, resulting in characteristic giant axonal swellings and progressive nerve dysfunction (Bomont et al., 2000). The therapeutic approach described involves gene replacement therapy, specifically using adeno-associated virus serotype 9 (AAV9) to deliver a functional copy of the GAN gene to deficient neurons (Taysha Gene Therapies, 2024). This intervention, such as the investigational drug TSHA-120, aims to restore gigaxonin levels to clear accumulated filaments and halt the progression of the disease (ClinicalTrials.gov, 2023).

Other names

Kelch-like protein 16KLHL16Giant axonal neuropathy proteinGAN1

Gene replacement therapy via adeno-associated virus (AAV) vector delivery to restore functional gigaxonin protein expression in deficient neurons.