@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}
}
