02652nas a2200277   4500008004100000245011100041210006900152260000900221300000700230490000700237520177100244653001002015653001702025653001002042653001602052653002202068653002002090653001202110653001402122653000802136653001602144100002802160700002902188700003602217856012102253       2021                        eng d00aExtracellular HDAC6 ZnF UBP domain modulates the actin network and post-translational modifications of Tau0 aExtracellular HDAC6 ZnF UBP domain modulates the actin network a  cMAY   a490 v193 a<p>Background: Microtubule-associated protein Tau undergoes aggregation in Alzheimer`s disease (AD) and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. Histone deacetylase-6 (HDAC6) plays an important role in aggresome formation, where it recruits polyubiquitinated aggregates to the motor protein dynein. Methods: Here, we have studied the effects of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3 beta regulation and cytoskeletal organization in neuronal cells by immunocytochemical analysis. This analysis reveals that the cell exposure to the UBP-type zinc finger domain of HDAC6 (HDAC6 ZnF UBP) can modulate Tau phosphorylation and actin cytoskeleton organization. Results: HDAC6 ZnF UBP treatment to cells did not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting the role of this domain in actin re-organization. Also, HDAC6 ZnF UBP treatment caused increase in nuclear localization of ApoE and tubulin localization in microtubule organizing centre (MTOC). Therefore, our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases. Upon HDAC6 ZnF UBP treatment, inactive phosphorylated form of GSK-3 beta increases without any change in total GSK-3 beta level. Conclusions: HDAC6 ZnF UBP was found to be involved in cytoskeletal re-organization by modulating actin dynamics and tubulin localization. Overall, our study suggests that ZnF domain of HDAC6 performs various regulatory functions apart from its classical function in aggresome formation in protein misfolding diseases.</p>10aActin10aCytoskeleton10aHDAC610aMicrotubule10aneurodegeneration10aPhosphorylation10aPodonut10aPodosomes10aTau10aTauopathies1 aBalmik, Abhishek, Ankur1 aSonawane, Shweta, Kishor1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/extracellular-hdac6-znf-ubp-domain-modulates-actin-network-and-post-translational01984nas a2200241   4500008004100000022001400041245007200055210006900127260000800196300001100204490000900215520126100224653001001485653001701495653001001512653001701522653001701539653000801556653001901564100002001583700003601603856010301639       2022                        eng d  a0167-488900aHistone deacetylase-6 modulates Tau function in Alzheimer's disease0 aHistone deacetylase6 modulates Tau function in Alzheimers diseas  cAUG  a1192750 v18693 a<p>
	Alzheimer's disease (AD), one of the major tauopathies, is multifactorial with a massive demand for disease modifying treatments rather than symptom management. An AD-affected neuron shows Tau depositions generated due to overload on the proteostasis machinery of the cell and/or abnormal post-translational modifications on Tau protein. Loss of memory or dementia is the most significant concern in AD, occurring due to the loss of neurons and the connections between them. In a healthy brain, neurons interact with the environment and each other through extensions and migratory structures. It can thus be safe to assume that Tau depositions affect these growth structures in neurons. A Histone Deacetylase, HDAC6, has shown elevated levels in AD while also demonstrating direct interaction with the Tau protein. HDAC6 interacts with multiple proteins in the cell and is possibly involved in various signalling pathways. Its deacetylase activity has been a point of controversy in AD; however other functional domains remain unexplored. This review highlights the beneficial potential of HDAC6 in AD in mediating both Tau proteostasis and cytoskeletal rewiring for the neuritic extensions through its Ubiquitin Binding domain (HDAC6 ZnF UBP).</p>
10aActin10aCytoskeleton10aHDAC610aMicrotubules10aProteostasis10aTau10aZnF UBP domain1 aQureshi, Tazeen1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/histone-deacetylase-6-modulates-tau-function-alzheimers-disease01751nas a2200241   4500008004100000022001400041245009800055210006900153260000800222300001100230490000800241520096100249653001001210653001901220653002801239653001001267653001701277653001401294653001201308100002801320700003601348856012501384       2022                        eng d  a0171-933500aInter-relationship of Histone Deacetylase-6 with Tau-cytoskeletal organization and remodeling0 aInterrelationship of Histone Deacetylase6 with Taucytoskeletal o  cAPR  a1512020 v1013 aCytoskeletal elements are the key players in cellular integrity, structure, signalling and migration. Each cytoskeletal element comprises of properties with respect to its structure and stability, which serve a specific array of functions. These structures are highly dynamic and regulated by modulation via direct interaction or post-translational modifications. HDAC6 is a cytoplasmic deacetylase known to regulate a wide range of cellular functions either through its deacetylase activity or direct interaction via its C-terminal ZnF UBP domain. HDAC6 has been widely studied for its role in aggresome formation, which acts as a protective mechanism upon protein aggregation. HDAC6 is known to play a critical role in the regulation of cytoskeletal elements-microtubules and actin filaments. This review summarizes the regulatory role of HDAC6 in cytoskeletal remodeling and dynamics of neuronal cells and its significance in neurodegenerative diseases.10aActin10aCell migration10aCytoskeleton remodeling10aHDAC610aMicrotubules10aPodosomes10aZnF UBP1 aBalmik, Abhishek, Ankur1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/inter-relationship-histone-deacetylase-6-tau-cytoskeletal-organization-and-remodeling