02270nas a2200217 4500008004100000022001400041245010100055210006900156260000800225300001200233490000700245520150100252653002201753653004401775653002301819653000801842653001601850100002901866700003601895856012101931 2018 eng d a0895-869600aPrion-like propagation of post-translationally modified tau in alzheimer's disease: a hypothesis0 aPrionlike propagation of posttranslationally modified tau in alz cAUG a480-4900 v653 a

The microtubule-associated protein Tau plays a key role in the neuropathology of Alzheimer's disease by forming intracellular neurofibrillary tangles. Tau in the normal physiological condition helps stabilize microtubules and transport. Tau aggregates due to various gene mutations, intracellular insults and abnormal post-translational modifications, phosphorylation being the most important one. Other modifications which alter the function of Tau protein are glycation, nitration, acetylation, methylation, oxidation, etc. In addition to forming intracellular aggregates, Tau pathology might spread in a prion-like manner as revealed by several in vitro and in vivo studies. The possible mechanism of Tau spread can be via bulk endocytosis of misfolded Tau species. The recent studies elucidating this mechanism have mainly focussed on the aggregation and spread of repeat domain of Tau in the cell culture models. Further studies are needed to elucidate the prion-like propagation property of full-length Tau and its aggregates in a more intense manner in vitro as well as in vivo conditions. Varied post-translational modifications can have discrete effects on aggregation propensity of Tau as well as its propagation. Here, we review the prion-like properties of Tau and hypothesize the role of glycation in prion-like properties of Tau. This post-translationally modified Tau might have an enhanced propagation property due to differential properties conferred by the modifications.

10aAlzheimer disease10aPost-translational modifications of tau10aPropagation of tau10aTau10aTauopathies1 aSonawane, Shweta, Kishor1 aChinnathambi, Subashchandrabose uhttps://library.ncl.res.in/content/prion-propagation-post-translationally-modified-tau-alzheimers-disease-hypothesis01813nas a2200157 4500008004100000245008600041210006900127260000900196300001600205490000600221520122900227100002901456700001701485700003601502856011701538 2019 eng d00aProtein-capped metal nanoparticles inhibit tau aggregation in alzheimer's disease0 aProteincapped metal nanoparticles inhibit tau aggregation in alz cJULY a12833-128400 v43 a

The Alzheimer's disease (AD) therapeutic research is yielding a large number of potent molecules. The nanoparticle-based therapeutics against the protein aggregation in AD is also taking a lead especially with amyloid-beta as a primary target. In this work, we have screened for the first time protein-capped (PC) metal nanoparticles for their potency in inhibiting Tau aggregation in vitro. We present a novel function of PC-Fe3O4 and PC-CdS nanoparticles as potent Tau aggregation inhibitors by fluorescence spectrometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and electron microscopy. We demonstrate that the biologically synthesized PC-metal nanoparticles, especially iron oxide do not affect the viability of neuroblastoma cells. Moreover, PC-CdS nanoparticles show dual properties of inhibition and disaggregation of Tau. Thus, the nanoparticles can take a lead as potent Tau aggregation inhibitors and can be modified for specific drug delivery due to their very small size. The current work presents unprecedented strategy to design anti-Tau aggregation drugs, which provides interesting insights to understand the role of biological nanostructures in Alzheimer's disease.
 

1 aSonawane, Shweta, Kishor1 aAhmad, Absar1 aChinnathambi, Subashchandrabose uhttps://library.ncl.res.in/content/protein-capped-metal-nanoparticles-inhibit-tau-aggregation-alzheimers-disease02201nas a2200205 4500008004100000022001400041245006800055210006500123260000800188300001000196490000700206520153200213653003601745653002401781653001201805653001801817100002901835700003601864856009501900 2020 eng d a1387-287700aP301 L, an FTDP-17 mutant, exhibits enhanced glycation in vitro0 aP301 L an FTDP17 mutant exhibits enhanced glycation in vitro cJAN a61-710 v753 a

Background: Frontotemporal dementia and parkinsonism-linked to chromosome-17 are a group of diseases with tau mutations leading to primary tauopathies which include progressive supranuclear palsy, corticobas al syndrome, and frontotemporal lobar degeneration. Alzheimer's disease is a non-primary tauopathy, which displays tau neuropathology of excess tangle formation and accumulation. FTDP-17 mutations are responsible for early onset of AD, which can be attributed to compromised physiological functions due to the mutations. Tau is a microtubule-binding protein that secures the integrity of polymerized microtubules in neuronal cells. It malfunctions owing to various insults and stress conditions-like mutations and post-translational modifications. Objective: In this study, we modified the wild type and tau mutants by methyl glyoxal and thus studied whether glycation can enhance the aggregation of predisposed mutant tau. Methods: Tau glycation was studied by fluorescence assays, SDS-PAGE analysis, conformational evaluation, and transmission electron microscopy. Results: Our study suggests that FTDP-17 mutant P301 L leads to enhanced glycation-induced aggregation as well as advanced glycation end products formation. Glycation forms amorphous aggregates of tau and its mutants without altering its native conformation. Conclusion: The metabolic anomalies and genetic predisposition have found to accelerate tau-mediated neurodegeneration and prove detrimental for the early-onset of Alzheimer's disease.

10aadvanced glycation end products10aAlzheimer's disease10aFTDP-1710atau glycation1 aSonawane, Shweta, Kishor1 aChinnathambi, Subashchandrabose uhttps://library.ncl.res.in/content/p301-l-ftdp-17-mutant-exhibits-enhanced-glycation-vitro