Human HDAC6 Active Enzyme
- Known as:
- Human HDAC6 Active Enzyme
- Catalog number:
- x1740e
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Exalpha
- Gene target:
- Human HDAC6 Active Enzyme
Related genes to: Human HDAC6 Active Enzyme
- Gene:
- HDAC6 NIH gene
- Name:
- histone deacetylase 6
- Previous symbol:
- -
- Synonyms:
- KIAA0901, JM21, HD6, FLJ16239, PPP1R90
- Chromosome:
- Xp11.23
- Locus Type:
- gene with protein product
- Date approved:
- 2000-11-28
- Date modifiied:
- 2015-09-11
Related products to: Human HDAC6 Active Enzyme
Related articles to: Human HDAC6 Active Enzyme
- Histone deacetylase 6 (HDAC6), a predominantly cytoplasmic deacetylase, has emerged as a critical regulator of protein homeostasis, and plays an important role in neurodegenerative disorders characterized by Tau pathology. We investigated the role of zinc-finger ubiquitin-binding domain (ZnF UBP) of HDAC6 in modulating tau structure and function. HDAC6 is well known for its deacetylase activity and involvement in aggresome formation but the functional contribution of its ZnF UBP domain in tau biology remains not well explored. Using a combination of biochemical, biophysical, and molecular approaches, we demonstrate that the ZnF UBP domain of HDAC6 directly interacts with tau, influencing its conformational dynamics and aggregation propensity. Our findings reveal that this interaction is independent of HDAC6's catalytic deacetylase activity, highlighting a non-canonical mechanism through which HDAC6 regulates tau. Structural analyses indicate that binding of ZnF UBP induces conformational rearrangements in tau, potentially altering its microtubule-binding capacity and aggregation behavior. Furthermore, we show that the HDAC6-tau interaction modulates tau aggregation, suggesting a protective or regulatory role in preventing aberrant tau aggregation. Functional assays support the notion that ZnF UBP-mediated modulation of tau contributes to maintaining cytoskeletal integrity and cellular proteostasis. These observations suggests that HDAC6 functions not only as a deacetylase but also performs regulatory functions through ZnF UBP domain that can influence the function and properties of intrinsically disordered proteins (IDPs) like tau. Overall, this chapter provides mechanistic insights into the non-enzymatic functions of HDAC6, specifically through its ZnF UBP domain, in regulating tau structure and function. Understanding this interaction expands the current perspective on HDAC6 biology and underscores its potential as a therapeutic target in tauopathies, including Alzheimer's disease and targeting domain-specific interactions of HDAC6 may offer a novel therapeutic strategy to modulate tau pathology. - Source: PubMed
Publication date: 2026/06/08
Balmik Abhishek AnkurChinnathambi Subashchandrabose - Development of Alzheimer's is promoted through the accumulation of Tau and Amyloid Beta (Aβ) proteins at various neuronal as well as glial junctions. Tau, a microtubule-associated protein, is localized at the axonal region of neurons under physiological conditions. The main function of Tau protein is to stabilize microtubules, mediated by the electrostatic interaction of their surface with the repeat domains of Tau. The post-translational modifications (PTMs) are necessary for the physiological functioning of protein, but upon abnormal phosphorylation of Tau, Neuro-fibrillary Tangles of protein are generated disrupting normal brain functionality. Cell migration is a physiological functioning of the cell necessary for various signalling from development, cellular communication, immune function etc. cellular microenvironment affect the behaviour of the cell, which can be detected by its migration propensity. The in vitro assays assist in understanding the adhesion, migration and invasion strategies of migratory cells in response to extracellular stimuli. The migration property can be linked to phenotypic changes of microglia as anti-inflammatory phenotype of microglia display increase migration and invasion, hence understanding migration propensity over Tau and HDAC6 exposure is necessary. - Source: PubMed
Publication date: 2026/07/02
Chinnathambi SubashchandraboseDesale Smita Eknath - This chapter pulls together current research on how HDAC shuttling between the nucleus and cytoplasm affects neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's, and epilepsy. It takes a close look at why these shifts in HDAC localization matter so much in brain disease and its implications for new treatments. Histone deacetylases (HDACs) are a big deal when it comes to gene regulation in the brain. They play key roles in both neurodegeneration and the brain's ability to adapt, working inside the nucleus and out in the cytoplasm. This chapter unpacks the molecular mechanisms behind HDAC trafficking-how they move around-highlights the different roles of HDAC isoforms, and compares localization-specific effects. It digs into how HDACs impact protein aggregation and synaptopathies. Some findings stand out: HDAC4 and HDAC1 are tightly controlled by phosphorylation signals, which change their cellular localization and influence neuronal mortality. For example, HDAC6 is majorly involved in cellular trafficking and clearing protein aggregates, whereas HDAC4 aggregation in the nucleus is responsible for driving neuronal toxicity. If HDAC1 undergoes nuclear export, it interacts with motor proteins to impact mitochondrial transport. Drugs that block HDAC6 look promising in preclinical models-they help restore neuronal transport systems and clear protein aggregation. Moving HDAC4 out of the nucleus seems to support better synaptic function and motor skills. As a general rule, HDAC accumulation in the nucleus shuts down genes that keep neurons alive, but keeping them in the cytoplasm helps preserve connections between neurons. You'll also find thorough, practical advice on how to study HDACs in brain research-covering everything from enzyme assays and cell experiments to live animal models, plasticity tracking, drug testing, and data analysis. A major innovation featured here is using CRISPR-based tricks to control exactly where HDACs go inside cells: forced targeting using dCas9 fusions, editing natural localization signals, and even using optogenetics for precise on-demand control. In short, the chapter is a hands-on guide for anyone trying to unravel HDAC mechanisms in diseases like Alzheimer's, Parkinson's, Huntington's, or in studies of brain plasticity. Some standout methods include tracking HDAC localization in the cells, measuring how phosphorylation affects their shuttling, and using HDAC2 inhibitors for cognitive boosts. It also covers isoform-specific approaches in Huntington's models, manipulating HDAC location with CRISPR for deeper insights, and combining live-cell imaging with biochemical and chromatin studies for robust validation. This chapter sheds light on the latest advances, with a strong focus on precision, quantitative results, and translating these findings into real-world applications. - Source: PubMed
Publication date: 2026/07/15
Mehta BhupeshNambiar SinjithaShirke OmkarPandita SatyarthMarkandeya Yogananda S - The class IIb histone deacetylase HDAC6 is responsible for the deacetylation of multiple cytoplasmic substrates, including α-tubulin and Miro-1, and has emerged as an important therapeutic target in neuropathies. In this context, several HDAC6 inhibitors effective in neuropathic models, exhibit slow-binding and slow-release behavior, thereby requiring kinetic approaches that extend beyond commonly used endpoint assays, which can lead to misinterpretation of inhibitor potency and mechanism of action. Notably, compounds with slow dissociation kinetics may offer improved therapeutic properties in neuropathic conditions, as sustained target engagement can translate into prolonged improvement of axonal transport and cytoskeletal dynamics. In this chapter, we outline a comprehensive methodology for the study of HDAC6 inhibition and the identification of slow-binding and slow-dissociating inhibitors. - Source: PubMed
Publication date: 2026/06/10
Cellupica EdoardoFossati GianlucaSteinkühler ChristianCaprini Gianluca - Epigenetic dysregulation is recognized as a primary contributor to the pathogenesis of neurodegenerative disorders, especially Alzheimer`s disease (AD). Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA regulation, govern gene expression without altering the DNA sequence, which plays a crucial role in neuronal development, synaptic plasticity, and memory formation. In AD, abnormal epigenetic alterations disrupt neuronal homeostasis, promote Aβ aggregation, tau hyperphosphorylation, and neuroinflammation, which leads to cognitive impairment. This chapter explores the assays performed and their processes using epigenetic modulators, along with their therapeutic potential in neurodegenerative diseases, especially AD. HDAC inhibitors, DNMT inhibitors, and emerging approaches, such as PROTACs for selective degradation of epigenetic enzymes, were discussed in the context of neurocognitive disorders. Preclinical and clinical evidence suggest that targeting specific HDAC isoforms (HDAC3, HDAC6, etc) can restore synaptic plasticity and improve cognitive function. This chapter further discusses recent advances, challenges in drug specificity, BBB permeability, and off-target epigenetic effects, which remain barriers to clinical translation. Case studies highlighting successful epigenetic interventions in AD models were presented to demonstrate therapeutic feasibility. Overall, epigenetic modulators present a promising therapeutic approach for neurodegeneration, and continued research integrating various assays like DNA methylation analysis, histone modification analysis, non-coding RNA analysis, neuroinflammation analysis, and functional and behavioral assays in AD models is significant in harnessing the full potential for AD treatment. - Source: PubMed
Publication date: 2026/07/15
Halder DebojyotiPrajapati DenishBanerjee TonmoyBiswas SwatiGhosh Balaram