Tubulin deacetylase NDST3 modulates lysosomal acidification: Implications in neurological diseases

Abstract

Neurological diseases (NDs), featured by progressive dysfunctions of the nervous system, have become a growing burden for the aging populations. N‐Deacetylase and N‐sulfotransferase 3 (NDST3) is known to catalyze deacetylation and N‐sulfation on disaccharide substrates. Recently, NDST3 is identified as a novel deacetylase for tubulin, and its newly recognized role in modulating microtubule acetylation and lysosomal acidification provides fresh insights into ND therapeutic approaches using NDST3 as a target. Microtubule acetylation and lysosomal acidification have been reported to be critical for activities in neurons, implying that the regulators of these two biological processes, such as the previously known microtubule deacetylases, histone deacetylase 6 (HDAC6) and sirtuin 2 (SIRT2), could play important roles in various NDs. Aberrant NDST3 expression or tubulin acetylation has been observed in an increasing number of NDs, including amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), schizophrenia and bipolar disorder, Alzheimer's disease (AD), and Parkinson's disease (PD), suggesting that NDST3 is a key player in the pathogenesis of NDs and may serve as a target for development of new treatment of NDs.

Sex‐specific genetic architecture of late‐life memory performance

“…One notable significant gene‐level association, NDST3 , contributed to the heparan sulfate pathway signal among females. NDST3 is involved in microtubule acetylation, and notably microtubule deacetylation is a hallmark of neurodegenerative disorders 51 . Indeed, atypical expression of NDST3 is observed in multiple neurodegenerative disorders, including AD 51 …”

“…NDST3 is involved in microtubule acetylation, and notably microtubule deacetylation is a hallmark of neurodegenerative disorders. 51 Indeed, atypical expression of NDST3 is observed in multiple neurodegenerative disorders, including AD. 51 …”

“…NDST3 is involved in microtubule acetylation, and notably microtubule deacetylation is a hallmark of neurodegenerative disorders. 51 Indeed, atypical expression of NDST3 is observed in multiple neurodegenerative disorders, including AD. 51 In a recent sex-aware AD endophenotype GWAS study by our group, we hypothesized that female-specific genomic findings may be driven by (1) X-chromosome, (2) sex hormones, or (3) both.…”

“…51 Indeed, atypical expression of NDST3 is observed in multiple neurodegenerative disorders, including AD. 51 In a recent sex-aware AD endophenotype GWAS study by our group, we hypothesized that female-specific genomic findings may be driven by (1) X-chromosome, (2) sex hormones, or (3) both. 15 Thus, it is note-worthy that we identified a hormone-related target (heparan sulfate signaling) and an X-chromosome candidate (EGFL6; Figure 3).…”

Iron oxide nanoparticles induce ferroptosis via the autophagic pathway by synergistic bundling with paclitaxel

“…Sequestosome1 (p62) is a multifunctional adapter protein that regulates the accumulation of protein aggregates and autophagic clearance (38). Histone deacetylase 6 (HDAC6) is a member of class IIb HDAC family and it deacetylates microtubule proteins, resulting in microtubule depolymerization and disconnection of the autophagosomal lysosomal fusion pathway (39)(40)(41), thereby inhibiting a member of the ATG8 family, LC3, which is a marker of the autophagic process. Moreover, the state of cellular redox homeostasis has a significant impact on autophagy (42).…”