Upregulation of SNAP25 by HDAC inhibition ameliorates Niemann‐Pick Type C disease phenotypes via autophagy induction

• Published in: Clinical and translational medicine 2022-04, Vol.12 (4), p.e776-n/a
• Main Authors: Jung 1,‡, Yooju, Lee 2,‡, Seung‐Eun, Kang, Insung, Cho, Sung Min, Kang, Kyung‐Sun, Kwon, Ho Jeong
• Format: Article
• Language: English
• Subjects: Autophagy; Biosynthesis; Cell cycle; Cell division; Cholesterol; Education; Gene expression; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylases; Humans; Letter to Editor; Metabolism; Metabolites; Niemann-Pick C1 Protein - genetics; Niemann-Pick Disease, Type C - drug therapy; Niemann-Pick Disease, Type C - genetics; Phenotype; Proteins; Signal transduction; Synaptosomal-Associated Protein 25 - genetics; Up-Regulation
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.776

Defective autophagy caused by the failure of autolysosome formation composed of SNARE machinery2 has been reported in NPC disease and synaptosomal-associated protein 25 (SNAP25) has been highlighted as one of the important components of SNARE machinery.3,4 Currently, there are no Food and Drug Administration (FDA)-approved treatments and a recent study shows that histone deacetylase (HDAC) inhibitors may be promising therapeutics for NPC disease.5 To investigate the effects of HDAC inhibition in NPC-iNSCs, suberoylanilide hydroxamic acid (SAHA), N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), FK228, and valproic acid (VPA) were treated at a non-toxic concentration (Figure S1A–E) and non-esterified cholesterol was stained with filipin III (Figure 1A,B). SEE PDF] TABLE 1 Number of gene list of 26 functional categories of eggNOG browser Functional categories NPC-SAHA NPC-HNHA (Number of genes/total number of genes) J Translation, ribosomal structure and biogenesis 4/462 2/462 A RNA processing and modification 10/246 15/246 K Transcription 64/1304 66/1304 L Replication, recombination and repair 5/318 7/318 B Chromatin structure and dynamics 11/271 10/271 D Cell cycle control cell division, chromosome partitioning 9/212 5/212 Y Nuclear structure 0/1 0/1 V Defense mechanisms 3/45 3/45 T Signal transduction mechanisms 66/964 48/964 M Cell wall/membrane/envelope biogenesis 1/58 2/58 N Cell motility 1/10 1/10 Z Cytoskeleton 39/494 25/494 W Extracellular stuructures 0/0 0/0 U Intracellular trafficking, secretion, and vesicular transport 189/2691 130/2691 O Posttranslational modification, protein turnover, chaperones 122/2068 86/2068 C Energy production and conversion 11/240 8/240 G Carbohydrate transport and metabolism 9/295 13/295 E Amino acid transport and metabolism 19/273 11/273 F Nucleotide transport and metabolism 9/124 3/124 H Coenzyme transport and metabolism 3/76 0/76 I Lipid transport and metabolism 14/320 6/320 P Inorganic ion transport and metabolism 25/285 14/285 Q Secondary metabolites biosynthesis, transport and catabolism 3/93 8/93 R General function prediction only 187/3964 196/3964 S Function unknown 184/3881 175/3881 NA Not assigned 416/41412 849/41412 Abbreviations: HNHA, N-hydroxy-7-(2-naphthylthio) heptanomide; NPC, Niemann–Pick Type C disease; SAHA, suberoylanilide hydroxamic acid. SEE PDF] Previous studies have reported that NPC-iNSCs are defective in neuronal differentiation.10 NPC-iNSCs exhibited reduced levels of TUJ1 (early neuron marker