01984nas 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-disease02282nas a2200241   4500008004100000022001400041245010000055210006900155260000800224300001100232490000800243520144900251653002001700653003801720653002501758653001701783653002001800100001601820700002001836700003601856700002601892856012201918       2024                        eng d  a0045-206800aMacrocyclic peptides derived from AcPHF6*and AcPHF6 to selectively modulate the Tau aggregation0 aMacrocyclic peptides derived from AcPHF6and AcPHF6 to selectivel  cOCT  a1076250 v1513 a<p>
	Ten macrocyclic peptides, each comprising 14 amino acids, were designed and synthesized based on the Tau aggregation model hexapeptides AcPHF6* and AcPHF6. The design took into account the aggregation tendencies of each residue in AcPHF6* and AcPHF6, their aggregation models, while employing peptide-based structural design principles including N-methylation to promote turns and to block hydrogen bond propagation and elongation of the aggregation chain. NMR analysis supported that all these peptides adopted an antiparallel beta-sheet conformation. Self-aggregation studies characterized the aggregation properties of these peptides, identifying two peptides with the highest (P3) and lowest (P8) aggregation tendencies. In cross-aggregation studies with the parent peptides AcPHF6* and AcPHF6, P3 and P8 were found to promote and reduce aggregation, respectively. Furthermore, P3 and P8 demonstrated an enhancement and diminution effect on the aggregation of K18wt, indicating their capacity to modulate aggregation even at the macromolecular level. Thus, the two simple peptides, P3 and P8 selectively exhibit pro- or anti-aggregation effects on PHF peptides and Tau. This study, has thus developed structurally well-defined non-complex peptides, derived from AcPHF6* and AcPHF6, to modulate Tau aggregation as desired, offering applications in Tau model studies and the development of Tau aggregation inhibitors or promoters.</p>
10aCyclic peptides10aPeptide -based drug design (PBDD)10aPeptide conformation10aPHF peptides10aTau Aggregation1 aDangi, Abha1 aQureshi, Tazeen1 aChinnathambi, Subashchandrabose1 aMarelli, Udaya, Kiran  uhttps://library.ncl.res.in/content/macrocyclic-peptides-derived-acphf6and-acphf6-selectively-modulate-tau-aggregation