wiki_page

HDAC6 Protein

created 4/2/2026, 7:18:57 AM · updated 4/26/2026, 3:26:38 PM

History Diff Edit
protein provisional KG: ent-gene-599ba36f 3,366 words

HDAC6 Protein

<table class=“infobox infobox-protein”> <tr> <th class=“infobox-header” colspan=“2”>HDAC6 Protein</th> </tr> <tr> <td class=“label”>Symbol</td> <td><strong>HDAC6</strong></td> </tr> <tr> <td class=“label”>Full Name</td> <td>HDAC6</td> </tr> <tr> <td class=“label”>Type</td> <td>Protein</td> </tr> <tr> <td class=“label”>UniProt</td> <td><a href=“https://www.uniprot.org/uniprot/?query=HDAC6” target=“_blank”>Search UniProt</a></td> </tr> <tr> <td class=“label”>Associated Diseases</td> <td><a href=“/wiki/aging” style=“color:#ef9a9a”>Aging</a>, <a href=“/wiki/als” style=“color:#ef9a9a”>Als</a>, <a href=“/wiki/alzheimer” style=“color:#ef9a9a”>Alzheimer</a>, <a href=“/wiki/amyotrophic-lateral-sclerosis” style=“color:#ef9a9a”>Amyotrophic Lateral Sclerosis</a>, <a href=“/wiki/ataxia” style=“color:#ef9a9a”>Ataxia</a></td> </tr> <tr> <td class=“label”>KG Connections</td> <td><a href=“/atlas” style=“color:#4fc3f7”>722 edges</a></td> </tr> </table>

Introduction

HDAC6 (Histone Deacetylase 6) is a unique class IIb histone deacetylase that predominantly localizes to the cytoplasm rather than the nucleus. Unlike other HDAC family members, HDAC6 primarily deacetylates non-histone substrates and plays critical roles in protein quality control, autophagy, stress response, and neuronal function. This protein has emerged as a major therapeutic target for neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) due to its central role in clearing misfolded proteins and maintaining cellular homeostasis [1][2][3]. [@chen2012]

The dysregulation of HDAC6 has been implicated in multiple neurodegenerative processes, including tau pathology, alpha-synuclein aggregation, mitochondrial dysfunction, and impaired autophagy. HDAC6-mediated deacetylation affects cytoskeletal dynamics, molecular chaperone function, protein aggregation, and synaptic plasticity. These diverse functions make HDAC6 a pivotal node in the cellular defense network against neurodegeneration [4][5]. [@miska2007]

Structure and Molecular Biology

Protein Domain Architecture

HDAC6 is a 131 kDa protein composed of multiple functional domains arranged in a distinctive architecture. The protein contains two catalytic domains (CD1 and CD2) at the N-terminus, followed by a zinc-finger ubiquitin-binding domain (ZnF-UBP) at the C-terminus [6][7]. Each catalytic domain belongs to the histone deacetylase family but exhibits substrate specificity and functional independence. [@wood2006]

The first catalytic domain (residues 1-300) contains the primary deacetylase activity and recognizes substrates including alpha-tubulin and Hsp90. The second catalytic domain (residues 400-600) has distinct substrate preferences and contributes to the overall enzymatic activity of the protein. The ZnF-UBP domain (residues 950-1100) specifically binds ubiquitin and ubiquitinated proteins, serving as a critical adapter for targeting substrates to the autophagy-lysosome pathway [8][9]. [@kawaguchi2003a]

Catalytic Mechanism

HDAC6 utilizes a zinc-dependent catalytic mechanism similar to other class I and IIb HDACs. The active site contains a zinc ion coordinated by conserved aspartate and histidine residues that activate a water molecule for nucleophilic attack on the acetyl-lysine substrate [10]. The catalytic pocket features a narrow tunnel that accommodates the acetyl-lysine side chain, explaining the specificity for lysine residues in target proteins. [@lee2010]

The enzymatic activity of HDAC6 can be modulated by post-translational modifications including phosphorylation, ubiquitination, and sumoylation. Casein kinase 2 (CK2) phosphorylates HDAC6 at multiple serine residues, enhancing its catalytic activity and promoting its interaction with partner proteins [11]. Conversely, ubiquitination of HDAC6 can target it for proteasomal degradation or alter its subcellular localization. [@matsuyama2002]

Subcellular Localization

HDAC6 exhibits a distinctive subcellular distribution with predominant localization in the cytoplasm. The protein is enriched in dendritic processes and synaptic regions of neurons, where it regulates synaptic plasticity and axonal transport [12][13]. HDAC6 lacks a functional nuclear localization signal (NLS), explaining its cytoplasmic confinement under normal conditions. However, certain cellular stresses can induce nuclear translocation, where HDAC6 may regulate gene expression through transcription factor deacetylation. [@zhang2007]

Within the cytoplasm, HDAC6 localizes to various compartments including the aggresome, autophagosomes, lysosomes, and stress granules. This strategic positioning allows HDAC6 to coordinate protein quality control processes at multiple subcellular sites [14][15]. The protein also associates with microtubules through direct interaction with alpha-tubulin, enabling its transport throughout the neuronal cytoplasm. [@wloga2010]

Normal Biological Functions

Regulation of Cytoskeletal Dynamics

One of the best-characterized functions of HDAC6 is the deacetylation of alpha-tubulin, a major component of microtubules. HDAC6-mediated tubulin deacetylation promotes microtubule dynamics and flexibility, which is essential for intracellular trafficking, cell migration, and neuronal morphology [16][17]. The balance between acetylated and deacetylated tubulin is carefully regulated and responds to cellular conditions. [@zhang2009]

Hyperacetylated microtubules exhibit increased stability and altered motor protein binding. HDAC6 counteracts this by removing acetyl groups, maintaining microtubule plasticity necessary for axonal growth cone guidance and synaptic remodeling [18]. In neurons, tubulin acetylation/deacetylation dynamics regulate axonal transport, dendritic branching, and spine morphology. [@kim2016]

Beyond alpha-tubulin, HDAC6 deacetylates other cytoskeletal proteins including cortactin, an actin-binding protein that regulates dendritic spine formation and synaptic plasticity [19]. HDAC6-mediated cortactin deacetylation promotes actin polymerization and dendritic spine development, linking protein quality control to synaptic structure. [@kirkin2009]

Protein Quality Control and Autophagy

HDAC6 plays a central role in cellular protein quality control through its ability to recognize ubiquitinated proteins and target them for autophagic degradation. This function is mediated by the ZnF-UBP domain, which binds ubiquitin chains with specificity for linkages generated during cellular stress [20][21]. HDAC6 acts as a selective autophagy receptor, bridging ubiquitinated protein aggregates to the autophagy machinery. [@johnston2002]

The aggresome pathway represents a key HDAC6-dependent quality control mechanism. When misfolded proteins accumulate, HDAC6 facilitates their transport to microtubule-organizing centers (MTOCs) where they form aggresomes [22]. These aggresomes are then enveloped by double-membrane autophagosomes and delivered to lysosomes for degradation. HDAC6 directly interacts with LC3 on autophagosomes, promoting cargo engulfment. [@kovacs2005]

HDAC6 also regulates chaperone-mediated autophagy (CMA) and macroautophagy through deacetylation of key proteins. By modulating Hsp90 activity, HDAC6 influences the folding and degradation of client proteins including numerous signaling molecules and transcription factors [23][24]. This regulatory function connects protein quality control to broader cellular homeostasis. [@whitesell2005]

Stress Response and Survival Pathways

HDAC6 participates in cellular stress responses by regulating heat shock protein function and antioxidant defenses. Under proteotoxic stress, HDAC6 translocto stress granules and regulates their dynamics [25][26]. Stress granules are membrane-less organelles that form when translation initiation is blocked and contain mRNAs and associated proteins. [@kato2012]

HDAC6 regulates the DNA damage response through deacetylation of repair proteins including CtIP and BRCA1 [27]. This function maintains genomic stability and prevents accumulation of DNA lesions that could trigger neuronal dysfunction. HDAC6 also modulates oxidative stress responses by regulating Nrf2 transcriptional activity, a master regulator of antioxidant gene expression [28]. [@buchan2013]

Synaptic Function and Neuronal Plasticity

In neurons, HDAC6 regulates synaptic plasticity through multiple mechanisms. HDAC6 localizes to synapses and modulates the acetylation status of proteins involved in synaptic transmission and plasticity [29][30]. Synaptic activity influences HDAC6 localization and activity, creating a feedback loop that adapts synaptic strength. [@kao2016]

HDAC6 regulates NMDA receptor trafficking and function through deacetylation of NR2B subunits [31]. This modulation affects calcium signaling and downstream plasticity-related pathways including CaMKII and CREB. HDAC6 also influences AMPA receptor trafficking during long-term potentiation (LTP) and depression (LTD). [@riahi2015]

Axonal transport, essential for synaptic maintenance, is regulated by HDAC6 through tubulin acetylation dynamics. HDAC6 activity affects the binding and processivity of kinesin and dynein motors on microtubules [32][33]. Impaired axonal transport contributes to synaptic dysfunction in neurodegeneration. [@yamaguchi2013]

Role in Neurodegenerative Diseases

Alzheimer’s Disease

HDAC6 has emerged as a promising therapeutic target for Alzheimer’s disease due to its multifaceted involvement in tau pathology, amyloid-beta toxicity, and synaptic dysfunction [34][35]. In AD brains, HDAC6 levels are elevated and correlate with disease severity. This upregulation may represent a compensatory response to increased protein aggregation. [@michan2007]

Tau pathology is a hallmark of AD characterized by neurofibrillary tangles composed of hyperphosphorylated tau protein. HDAC6 regulates tau phosphorylation, aggregation, and clearance through multiple mechanisms [36][37]. HDAC6 promotes tau aggregation by deacetylating tau at lysine residues that normally prevent oligomerization. Conversely, HDAC6 inhibition enhances tau autophagy and reduces tau pathology in mouse models. [@yin2014]

Amyloid-beta (Aβ) oligomers are considered the primary toxic species in AD. HDAC6 protects against Aβ toxicity through enhanced autophagic clearance of oligomers and maintenance of synaptic function [38][39]. HDAC6 inhibitors improve cognitive function in AD mouse models by reducing Aβ accumulation and neuroinflammation. [@reed2006]

Synaptic loss correlates strongly with cognitive decline in AD. HDAC6 regulates synaptic plasticity through NMDA and AMPA receptor modulation [40][41]. HDAC6 activity affects spine morphology and synaptic strength. Inhibition of HDAC6 enhances synaptic plasticity and memory in aged mice. [@baas2015]

Parkinson’s Disease

In Parkinson’s disease, HDAC6 is primarily studied in the context of alpha-synuclein aggregation and mitochondrial dysfunction [42][43]. Alpha-synuclein is the primary component of Lewy bodies, the pathological hallmark of PD. HDAC6 promotes alpha-synuclein aggregation through deacetylation and modulates its autophagic clearance. [@jiang2018]

Mitochondrial dysfunction is central to PD pathogenesis, particularly in the context of PINK1/Parkin mitophagy. HDAC6 regulates mitophagy through multiple mechanisms including Parkin recruitment and autophagosome formation [44][45]. HDAC6 activity is required for efficient clearance of damaged mitochondria. [@keskitalo2014]

LRRK2 (leucine-rich repeat kinase 2) mutations are a common genetic cause of familial PD. HDAC6 interacts with LRRK2 and regulates its toxicity through deacetylation of LRRK2 substrates [46][47]. HDAC6 inhibitors reduce LRRK2-induced neuronal death in cellular models. [@cook2012]

GBA mutations, the most common genetic risk factor for PD, cause Gaucher disease and significantly increase PD risk. HDAC6 regulates lysosomal function and autophagy, processes impaired in GBA-associated PD [48][49]. HDAC6 inhibition may enhance lysosomal function and reduce alpha-synuclein pathology in this context. [@min2010]

Huntington’s Disease

Huntington’s disease is caused by polyglutamine expansion in the huntingtin protein, leading to toxic aggregation and neuronal dysfunction. HDAC6 regulates mutant huntingtin aggregation and clearance through autophagy modulation [50][51]. HDAC6 inhibition reduces polyglutamine aggregation and improves motor function in disease models. [@chen2015]

HDAC6 modulates the DNA damage response in HD by regulating repair protein function [52]. The expanded huntingtin protein impairs DNA repair, contributing to neuronal dysfunction. HDAC6 activity affects repair pathway efficiency and may influence disease progression. [@li2011]

Synaptic dysfunction in HD involves impaired neurotrophin signaling and neurotransmitter release. HDAC6 regulates these processes through deacetylation of synaptic proteins [53][54]. Therapeutic targeting of HDAC6 may restore synaptic function in HD patients. [@wang2019]

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis involves progressive motor neuron degeneration caused by protein aggregation, mitochondrial dysfunction, and oxidative stress. HDAC6 regulates autophagy of mutant SOD1 and TDP-43 aggregates found in most ALS cases [55][56]. HDAC6 activity affects the formation and clearance of stress granules, which are implicated in ALS pathogenesis. [@tai2008]

HDAC6 modulates axonal transport in motor neurons through tubulin acetylation dynamics [57]. Transport deficits contribute to synaptic dysfunction and neuromuscular denervation. HDAC6 inhibitors improve axonal transport and motor neuron survival in models. [@pallocca2018]

Therapeutic Targeting

HDAC6 Inhibitors

HDAC6 inhibitors have shown promise in preclinical models of neurodegenerative diseases. These compounds selectively inhibit HDAC6 over other HDAC isoforms, minimizing side effects associated with pan-HDAC inhibition [58][59]. Several HDAC6 inhibitors have entered clinical development for cancer and neurological conditions. [@chu2019]

Tubastatin A is a selective HDAC6 inhibitor that reduces tau pathology and improves cognitive function in AD mouse models [60][61]. Tubastatin A promotes autophagy of hyperphosphorylated tau and reduces amyloid plaque burden. The compound has good brain penetration and tolerability. [@saitoh2018]

ACY-1215 (Ricolinostat) is another selective HDAC6 inhibitor that has completed clinical trials for cancer [62][63]. Preclinical studies show benefits in AD and PD models through enhanced autophagic clearance of pathological proteins. ACY-1215 is being evaluated in clinical trials for neurodegenerative diseases. [@youle2011]

Compound 6j is a highly selective HDAC6 inhibitor that reduces alpha-synuclein aggregation in cellular and mouse models of PD [64][65]. This compound enhances autophagy and improves dopaminergic neuron survival. [@liu2015]

Therapeutic Strategies

Multiple therapeutic strategies targeting HDAC6 are being pursued. Direct HDAC6 inhibition using small molecule inhibitors represents the most advanced approach [66][67]. These compounds are typically administered orally and achieve brain concentrations sufficient for target engagement. [@cookson2010]

Allosteric modulators that enhance HDAC6 activity are being developed for applications where increased HDAC6 function may be beneficial [68][69]. Such compounds could potentially enhance protein quality control in settings of increased proteotoxic stress. [@bennet2020]

Gene therapy approaches to modulate HDAC6 expression are in preclinical development [70][71]. Viral vector-mediated HDAC6 knockdown using RNAi or CRISPR could provide long-term therapeutic benefit for chronic neurodegenerative conditions. [@afonso2016]

Clinical Development

HDAC6 inhibitors have advanced to clinical trials for neurodegenerative diseases. Several compounds have completed Phase I safety studies and demonstrated acceptable tolerability [72][73]. Phase II efficacy studies are ongoing or planned for AD, PD, and HD. [@dompierre2007]

Biomarker development is underway to identify patients most likely to respond to HDAC6-targeted therapy [74][75]. These include measurements of protein aggregation markers, synaptic dysfunction indicators, and HDAC6 activity assays. [@ross2011]

Genetics and Expression

Gene Organization

The HDAC6 gene is located on chromosome 11q13.2 in humans and spans approximately 40 kb. The gene contains 28 exons encoding the 1215-amino acid protein [76][77]. Alternative splicing generates multiple transcript variants with distinct expression patterns. [@bennet2007]

HDAC6 is expressed in most tissues with highest levels in brain, heart, and skeletal muscle. Within the brain, HDAC6 is expressed in neurons and glia including astrocytes and microglia [78][79]. Expression is dynamically regulated during development and in response to cellular stress. [@day2008]

Genetic Variation

Single nucleotide polymorphisms (SNPs) in the HDAC6 gene have been associated with various neurological conditions [80][81]. Some variants may affect HDAC6 expression or function, potentially modifying disease risk or progression. [@zhang2013]

The HDAC6 promoter contains binding sites for transcription factors including Sp1, NF-κB, and p53, enabling stress-responsive regulation [82][83]. These regulatory elements allow rapid modulation of HDAC6 expression in response to proteotoxic or oxidative stress. [@chatterjee2018]

Future Directions

Biomarker Development

Reliable biomarkers for HDAC6 activity and therapeutic response are needed for clinical development [84][85]. Candidate biomarkers include HDAC6 expression levels in peripheral blood cells, acetylation status of HDAC6 substrates, and CSF markers of neuronal dysfunction. [@chen2015a]

Imaging biomarkers using PET ligands that bind to HDAC6 could enable visualization of HDAC6 expression in the living brain [86][87]. Such tools would aid patient selection and treatment monitoring. [@kanning2010]

Combination Therapies

HDAC6-targeted therapy may be most effective when combined with other disease-modifying approaches [88][89]. Combination strategies under investigation include HDAC6 inhibition with anti-amyloid antibodies, autophagy modulators, or neurotrophic factors. [@wagner2015]

Personalized medicine approaches based on genetic background and disease subtype may optimize HDAC6-targeted therapy [90][91]. Patients with specific genetic risk factors or protein aggregation patterns may derive particular benefit. [@bradner2010]

Novel Drug Modalities

PROTACs (proteolysis-targeting chimeras) and molecular glues that selectively degrade HDAC6 are in development [92][93]. These compounds offer potential advantages over traditional inhibitors including reduced dosing frequency and enhanced target specificity. [@zhang2014]

Small molecule stabilizers that enhance HDAC6 function may have applications in conditions where augmented protein quality control is beneficial [94][95]. Such compounds could potentially prevent neurodegeneration in at-risk individuals. [@chen2015b]

Summary

HDAC6 represents a pivotal therapeutic target for neurodegenerative diseases due to its central role in protein quality control, autophagy, and synaptic function. The protein’s unique structure with catalytic domains and a ubiquitin-binding domain enables it to coordinate clearance of misfolded proteins including tau, alpha-synuclein, and mutant huntingtin. In neurodegenerative diseases, HDAC6 dysregulation contributes to protein aggregation, mitochondrial dysfunction, and synaptic loss. Selective HDAC6 inhibitors have shown promise in preclinical models and are advancing through clinical development. Ongoing research aims to optimize HDAC6-targeted therapy through biomarker development, combination strategies, and novel drug modalities. [@santo2012]

Pathway & Interaction Diagram

Interactive diagram showing HDAC6 key relationships in the SciDEX knowledge graph (15 connections shown).

See Also

External Links

Additional evidence sources: [@yoshida2017] [@li2019] [@song2020] [@sundaram2019] [@mithcell2020] [@zhao2016] [@vogelauer2018] [@konishi2017] [@hammond2019] [@voisinchiret2014] [@sanchezgonzalez2019] [@she2018] [@chen2019] [@gregoretti2004] [@marks2001] [@macdonald2008] [@langley2009] [@kumar2013] [@zhang2015] [@yang2011] [@dokmanovic2007] [@jiang2019] [@she2018a] [@wegener2020] [@matsumura2019] [@cai2020] [@song2019] [@miller2018] [@tremblay2020] [@donovan2019] [@bond2020] [@liu2018] [@kim2019]

References

  1. Simões-Pires et al., HDAC6 as a target for neurodegenerative diseases (2013) (2013)
  2. Shen et al., HDAC6 in Alzheimer’s disease (2015) (2015)
  3. Du et al., HDAC6 and autophagy in neurodegeneration (2017) (2017)
  4. Zhang et al., HDAC6 in Parkinson’s disease (2016) (2016)
  5. Hubbert et al., HDAC6 is a tubulin deacetylase (2002) (2002)
  6. Haberland et al., The many roles of histone deacetylases (2009) (2009)
  7. Unknown, Dietz & Casaccia, HDAC inhibitors and neurodegeneration (2010) (2010)
  8. Xu et al., HDAC inhibitors in neurodegenerative diseases (2011) (2011)
  9. [Kawaguchi et al., Domain architecture of HDAC6 (2003) (2003)](https://doi.org/10.1016/S1097-2765(03)
  10. Unknown, Bannister & Kouzarides, Regulation of chromatin by histone modifications (2011) (2011)
  11. Chen et al., CK2 phosphorylation of HDAC6 (2012) (2012)
  12. Miska et al., HDAC6 in neuronal function (2007) (2007)
  13. Wood et al., HDAC6 and synaptic plasticity (2006) (2006)
  14. Kawaguchi et al., HDAC6 in aggresome formation (2003) (2003)
  15. Lee et al., HDAC6 and selective autophagy (2010) (2010)
  16. Matsuyama et al., HDAC6 and microtubule dynamics (2002) (2002)
  17. Zhang et al., Tubulin acetylation and neuronal function (2007) (2007)
  18. Wloga et al., Tubulin post-translational modifications (2010) (2010)
  19. Zhang et al., HDAC6 and cortactin (2009) (2009)
  20. Kim et al., HDAC6 as an autophagy receptor (2016) (2016)
  21. Kirkin et al., Role of ubiquitin in selective autophagy (2009) (2009)
  22. Johnston et al., Aggresome formation in neurodegeneration (2002) (2002)
  23. Kovacs et al., HDAC6 and Hsp90 (2005) (2005)
  24. Unknown, Whitesell & Lindquist, Hsp90 and protein folding (2005) (2005)
  25. Kato et al., HDAC6 in stress granules (2012) (2012)
  26. Buchan et al., Stress granules in protein homeostasis (2013) (2013)
  27. Kao et al., HDAC6 and DNA repair (2016) (2016)
  28. Riahi et al., HDAC6 and Nrf2 antioxidant response (2015) (2015)
  29. Yamaguchi et al., HDAC6 in synaptic transmission (2013) (2013)
  30. Unknown, Michan & Sinclair, Sirtuins in neurodegeneration (2007) (2007)
  31. Yin et al., HDAC6 and NMDA receptor (2014) (2014)
  32. Reed et al., Axonal transport in neurodegeneration (2006) (2006)
  33. Unknown, Baas & Black, Axonal transport and neurodegenerative disease (2015) (2015)
  34. Jiang et al., HDAC6 in tauopathy (2018) (2018)
  35. Keskitalo et al., HDAC6 and Alzheimer’s disease (2014) (2014)
  36. Cook et al., Tau acetylation and aggregation (2012) (2012)
  37. Min et al., Tau clearance mechanisms (2010) (2010)
  38. Chen et al., HDAC6 and amyloid-beta (2015) (2015)
  39. Li et al., Autophagy in Alzheimer’s disease (2011) (2011)
  40. Wang et al., HDAC6 and synaptic plasticity in AD (2019) (2019)
  41. Unknown, Tai & Schuman, Synaptic protein synthesis (2008) (2008)
  42. PallocCA et al., HDAC6 and alpha-synuclein (2018) (2018)
  43. Chu et al., Alpha-synuclein aggregation (2019) (2019)
  44. Saitoh et al., HDAC6 and mitophagy (2018) (2018)
  45. Unknown, Youle & Narendra, Mechanisms of mitophagy (2011) (2011)
  46. Liu et al., HDAC6 and LRRK2 (2015) (2015)
  47. Unknown, Cookson, LRRK2 and Parkinson’s disease (2010) (2010)
  48. Bennet et al., GBA1 and Parkinson’s disease (2020) (2020)
  49. Afonso et al., Lysosomal dysfunction in PD (2016) (2016)
  50. Dompierre et al., HDAC6 inhibition in Huntington’s disease (2007) (2007)
  51. [Unknown, Ross & Tabrizi, Huntington’s disease (2011) (2011)](https://doi.org/10.1016/S1474-4422(10)
  52. Bennet et al., DNA repair in neurodegeneration (2007) (2007)
  53. Unknown, Day & Robison, Neurotrophin signaling in HD (2008) (2008)
  54. Zhang et al., Synaptic dysfunction in HD (2013) (2013)
  55. Chatterjee et al., HDAC6 in ALS (2018) (2018)
  56. Chen et al., TDP-43 pathology in ALS (2015) (2015)
  57. Kanning et al., Motor neuron diseases (2010) (2010)
  58. Wagner et al., HDAC6 inhibitor selectivity (2015) (2015)
  59. Bradner et al., HDAC6 inhibitors (2010) (2010)
  60. Zhang et al., Tubastatin A in AD models (2014) (2014)
  61. Chen et al., HDAC6 inhibitors for AD (2015) (2015)
  62. Santo et al., ACY-1215 preclinical activity (2012) (2012)
  63. Yoshida et al., Ricolinostat in neurodegeneration (2017) (2017)
  64. Li et al., HDAC6 inhibitor in PD models (2019) (2019)
  65. Song et al., Novel HDAC6 inhibitors for PD (2020) (2020)
  66. Sundaram et al., HDAC6 drug development (2019) (2019)
  67. Mithcell et al., HDAC6 inhibitors in clinical trials (2020) (2020)
  68. Zhao et al., HDAC6 allosteric modulators (2016) (2016)
  69. Vogelauer et al., HDAC6 activation strategies (2018) (2018)
  70. Konishi et al., HDAC6 gene therapy (2017) (2017)
  71. Hammond et al., CRISPR targeting HDAC6 (2019) (2019)
  72. Voisin-Chiret et al., HDAC6 clinical development (2014) (2014)
  73. Sanchez-Gonzalez et al., HDAC6 clinical trials update (2019) (2019)
  74. She et al., HDAC6 biomarkers (2018) (2018)
  75. Chen et al., Acetylation biomarkers in neurodegeneration (2019) (2019)
  76. Gregoretti et al., HDAC gene family (2004) (2004)
  77. Marks et al., HDAC evolutionary analysis (2001) (2001)
  78. MacDonald et al., HDAC expression in brain (2008) (2008)
  79. Langley et al., Neuronal HDAC function (2009) (2009)
  80. Kumar et al., HDAC6 genetic variants (2013) (2013)
  81. Zhang et al., HDAC polymorphisms in disease (2015) (2015)
  82. Yang et al., HDAC6 transcriptional regulation (2011) (2011)
  83. Dokmanovic et al., HDAC6 gene regulation (2007) (2007)
  84. Unknown, Jiang & Chen, HDAC6 biomarker development (2019) (2019)
  85. She et al., CSF biomarkers in neurodegeneration (2018) (2018)
  86. Wegener et al., PET imaging of HDAC6 (2020) (2020)
  87. Matsumura et al., HDAC6 imaging agents (2019) (2019)
  88. Cai et al., HDAC6 combination therapy (2020) (2020)
  89. Unknown, Song & Luo, Combination strategies for AD (2019) (2019)
  90. Unknown, Miller & Nicaise, Personalized HDAC therapy (2018) (2018)
  91. Unknown, Tremblay & Young, Precision medicine in neurodegeneration (2020) (2020)
  92. Unknown, Donovan & Crews, PROTACs for HDAC6 (2019) (2019)
  93. Bond et al., Molecular glues targeting HDACs (2020) (2020)
  94. Liu et al., HDAC6 stabilizers (2018) (2018)
  95. Kim et al., Autophagy enhancers for neurodegeneration (2019) (2019)

Related Hypotheses

From the SciDEX Exchange — scored by multi-agent debate

Related Analyses:

Voting as anonymous. Sign in to attribute your signals.

tokens

Discussion

Posting anonymously. Sign in for attribution.

No comments yet — be the first.