@article {46847,
	title = {Role of microglia in regulating cholesterol and tau pathology in alzheimer{\textquoteright}s disease},
	journal = {Cellular and Molecular Neurobiology},
	year = {2020},
	month = {MAY},
	type = {Review; Early Access 2020},
	abstract = {<p>Cholesterol, a principal constituent of the cell membrane, plays a crucial role in the brain by regulating the synaptic transmission, neuronal signaling, as well as neurodegenerative diseases. Defects in the cholesterol trafficking are associated with enhanced generation of hyperphosphorylated Tau and Amyloid-beta protein. Tau, a major microtubule-associated protein in the brain, is the key regulator of the mature neuron. Abnormally hyperphosphorylated Tau hampers the major functions related to microtubule assembly by promoting neurofibrillary tangles of paired helical filaments, twisted ribbons, and straight filaments. The observed pathological changes due to impaired cholesterol and Tau protein accumulation cause Alzheimer{\textquoteright}s disease. Thus, in order to regulate the pathogenesis of Alzheimer{\textquoteright}s disease, regulation of cholesterol metabolism, as well as Tau phosphorylation, is essential. The current review provides an overview of (1) cholesterol synthesis in the brain, neurons, astrocytes, and microglia; (2) the mechanism involved in modulating cholesterol concentration between the astrocytes and brain; (3) major mechanisms involved in the hyperphosphorylation of Tau and amyloid-beta protein; and (4) microglial involvement in its regulation. Thus, the answering key questions will provide an in-depth information on microglia involvement in managing the pathogenesis of cholesterol-modulated hyperphosphorylated Tau protein.</p>
},
	keywords = {Alzheimer{\textquoteright}s disease, Amyloid-beta protein, Cholesterol, microglia, Tau hyperphosphorylation},
	issn = {0272-4340},
	doi = {10.1007/s10571-020-00883-6},
	author = {Nanjundaiah, Shwetha and Chidambaram, Hariharakrishnan and Chandrashekar, Madhura and Chinnathambi, Subashchandrabose}
}
@article {46609,
	title = {Role of cysteines in accelerating Tau filament formation},
	journal = {Journal of Biomolecular Structure \& Dynamics},
	volume = {40},
	year = {2022},
	month = {JUN},
	pages = {4366-4375},
	type = {Article},
	abstract = {<p>
	Alzheimer{\textquoteright}s disease is majorly associated with intracellular accumulation of Tau into paired helical filaments and tangles. The self-aggregated dimeric and oligomeric species of Tau formed are more toxic to neuronal cells and acts as seeds for filament formation. The two cysteine residues and the two hexapeptide regions of full-length Tau play a key role in initialization and filament formation during Tau aggregation. The role of cysteine residues in Tau aggregation has been studied by in-vitro aggregation assay that was measured by Thioflavin S fluorescence to observe the kinetics of aggregation. In this study, we have performed in-vitro aggregation assay with recombinant full-length Tau and the cysteine mutants to understand the mechanism of cysteine independent Tau aggregation. Here, we report that cysteine mutant full-length Tau can aggregate to form filaments under in-vitro conditions. To visualize the polymorphisms of Tau and cysteine mutants under different aggregation conditions anionic cofactor, heparin was employed. Wild-type Tau showed rapid aggregation to form oligomers and filaments. On the other hand, the cysteine mutant delayed the initial Tau aggregation. This indicates the importance of cysteine residues in accelerating initial Tau nucleation for its aggregation. The filament morphology of wild-type and cysteine mutant Tau has been characterized using transmission electron microscopy and high-resolution transmission electron microscopy. Communicated by Ramaswamy H. Sarma</p>
},
	keywords = {Heparin-induced aggregation, Paired helical filaments, Tau Aggregation, Tau Oligomers, tau protein},
	issn = {0739-1102},
	doi = {10.1080/07391102.2020.1856720},
	author = {Chidambaram, Hariharakrishnan and Chinnathambi, Subashchandrabose}
}
