02651nas a2200277   4500008004100000245011100041210006900152260000900221300000700230490000700237520177100244653001002015653001702025653001002042653001602052653002202068653002002090653001202110653001402122653000802136653001602144100002802160700002902188700003602217856012002253       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  uhttp://library.ncl.res.in/content/extracellular-hdac6-znf-ubp-domain-modulates-actin-network-and-post-translational02403nas a2200217   4500008004100000245009700041210006900138260000900207300000700216490000700223520165600230653001601886653001601902653001601918653002301934653003701957653000801994100002802002700003602030856011902066       2021                        eng d00aMethylation as a key regulator of Tau aggregation and neuronal health in Alzheimer's disease0 aMethylation as a key regulator of Tau aggregation and neuronal h  cMAY   a510 v193 a<p>Neurodegenerative diseases like Alzheimer's, Parkinson's and Huntington's disease involves abnormal aggregation and accumulation of toxic proteins aggregates. Post-translational modifications (PTMs) of the causative proteins play an important role in the etiology of disease as they could either slow down or accelerate the disease progression. Alzheimer disease is associated with the aggregation and accumulation of two major protein aggregates-intracellular neurofibrillary tangles made up of microtubule-associated protein Tau and extracellular Amyloid-beta plaques. Post-translational modifications are important for the regulation of Tau`s function but an imbalance in PTMs may lead to abnormal Tau function and aggregation. Tau methylation is one of the important PTM of Tau in its physiological state. However, the methylation signature on Tau lysine changes once it acquires pathological aggregated form. Tau methylation can compete with other PTMs such as acetylation and ubiquitination. The state of PTM at these sites determines the fate of Tau protein in terms of its function and stability. The global methylation in neurons, microglia and astrocytes are involved in multiple cellular functions involving their role in epigenetic regulation of gene expression via DNA methylation. Here, we have discussed the effect of methylation on Tau function in a site-specific manner and their cross-talk with other lysine modifications. We have also elaborated the role of methylation in epigenetic aspects and neurodegenerative conditions associated with the imbalance in methylation metabolism affecting global methylation state of cells.</p>10aAggregation10aEpigenetics10amethylation10aMethyltransferases10apost-translational modifications10aTau1 aBalmik, Abhishek, Ankur1 aChinnathambi, Subashchandrabose  uhttp://library.ncl.res.in/content/methylation-key-regulator-tau-aggregation-and-neuronal-health-alzheimers-disease