@article {47016,
	title = {P301 L, an FTDP-17 mutant, exhibits enhanced glycation in vitro},
	journal = {Journal of Alzheimers Disease},
	volume = {75},
	year = {2020},
	month = {JAN},
	pages = {61-71},
	type = {Article},
	abstract = {<p>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{\textquoteright}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{\textquoteright}s disease.</p>
},
	keywords = {advanced glycation end products, Alzheimer{\textquoteright}s disease, FTDP-17, tau glycation},
	issn = {1387-2877},
	doi = {10.3233/JAD-191348},
	author = {Sonawane, Shweta Kishor and Chinnathambi, Subashchandrabose}
}
@article {47069,
	title = {Baicalein inhibits heparin-induced Tau aggregation by initializing non-toxic Tau oligomer formation},
	journal = {Cell Communication and Signaling},
	volume = {19},
	year = {2021},
	month = {FEB },
	pages = {16},
	type = {Article},
	abstract = {<p>Background: Amyloid aggregate deposition is the key feature of Alzheimer{\textquoteright}s disease. The proteinaceous aggregates found in the afflicted brain are the intra-neuronal neurofibrillary tangles formed by the microtubule-associated protein Tau and extracellular deposits, senile plaques, of amyloid beta (A beta) peptide proteolytically derived from the amyloid precursor protein. Accumulation of these aggregates has manifestations in the later stages of the disease, such as memory loss and cognitive inabilities originating from the neuronal dysfunction, neurodegeneration, and brain atrophy. Treatment of this disease at the late stages is difficult, and many clinical trials have failed. Hence, the goal is to find means capable of preventing the aggregation of these intrinsically disordered proteins by inhibiting the early stages of their pathological transformations. Polyphenols are known to be neuroprotective agents with the noticeable potential against many neurodegenerative diseases, such as Alzheimer{\textquoteright}s, Parkinson{\textquoteright}s, and Prion diseases. Methods: We analyzed the capability of Baicalein to inhibit aggregation of human Tau protein by a multifactorial analysis that included several biophysical and biochemical techniques. Results: The potency of Baicalein, a polyphenol from the Scutellaria baicalensis Georgi, against in vitro Tau aggregation and PHF dissolution has been screened and validated. ThS fluorescence assay revealed the potent inhibitory activity of Baicalein, whereas ANS revealed its mechanism of Tau inhibition viz. by oligomer capture and dissociation. In addition, Baicalein dissolved the preformed mature fibrils of Tau thereby possessing a dual target action. Tau oligomers formed by Baicalein were non-toxic to neuronal cells, highlighting its role as a potent molecule to be screened against AD. Conclusion: In conclusion, Baicalein inhibits aggregation of hTau40 by enhancing the formation of SDS-stable oligomers and preventing fibril formation. Baicalein-induced oligomers do not affect the viability of the neuroblastoma cells. Therefore, Baicalein can be considered as a lead molecule against Tau pathology in AD.</p>
},
	keywords = {Alzheimer{\textquoteright}s disease, Baicalein, Tau dissolution, Tau inhibition, Tau Oligomers},
	doi = {10.1186/s12964-021-00704-3},
	author = {Sonawane, Shweta Kishor and Uversky, Vladimir N. and Chinnathambi, Subashchandrabose}
}
