02148nas a2200301   4500008004100000022001400041245013100055210006900186260000800255300001100263490000800274520114300282653002001425653002501445653001701470653003501487653001901522653001301541653001201554653001401566653002001580100002101600700002201621700002101643700002501664700002501689856013201714       2020                        eng d  a0306-987700aPossible role of glycation in the regulation of amyloid beta precursor protein processing leading to amyloid beta accumulation0 aPossible role of glycation in the regulation of amyloid beta pre  cSEP  a1097990 v1423 a<p>Alzheimer's disease (AD) is one of the most common forms of neurodegenerative diseases amongst the aged population. The disease is multifactorial, and diabetes has been considered as one of the major risk factors for the development of AD. Chronic hyperglycemic condition in diabetes promotes non-enzymatic protein modification by glucose termed as glycation, which affects protein structure and function. Previous studies have shown that many of the enzymes, including proteases, are affected by glycation. Conversely, glycated proteins are known to become resistant to protease action. In these hypotheses, we have extended these two concepts to the regulation of amyloid-beta protein precursor (A beta PP) by secretases leading to amyloid-beta (Af3) accumulation. The first hypothesis deals with the glycation of alpha-secretases leading to its reduced activity, while in the second hypothesis, A beta PP glycation may prevent a-secretases action, rendering its processing by beta secretase. As diabetes is a risk factor for the development of AD, either or both these pathways may operate, leading to the manifestation of AD.</p>
10aAlpha-secretase10aAlzheimer `s disease10aAmyloid-beta10aAmyloid-beta protein precursor10aBeta-secretase10aDiabetes10aglucose10aGlycation10aType-3 diabetes1 aPatil, Gouri, V.1 aJoshi, Rakesh, S.1 aKazi, Rubina, S.1 aKulsange, Shabda, E.1 aKulkarni, Mahesh, J.  uhttps://library.ncl.res.in/content/possible-role-glycation-regulation-amyloid-beta-precursor-protein-processing-leading-amyloid02075nas a2200229   4500008004100000022001400041245011200055210006900167260000800236300001100244490000900255520129500264653002501559653001401584653001401598653001301612653001901625100003601644700001601680700002601696856012301722       2023                        eng d  a0167-488900aTau aggregates improve the Purinergic receptor P2Y12-associated podosome rearrangements in microglial cells0 aTau aggregates improve the Purinergic receptor P2Y12associated p  cJUN  a1194770 v18703 a<p>
	Alzheimer's disease (AD) is a progressive neurodegenerative disease that is associated with protein misfolding, plaque accumulation, neuronal dysfunction, synaptic loss, and cognitive decline. The pathological cascade of AD includes the intracellular Tau hyperphosphorylation and its subsequent aggregation, extracellular Amyloid-&amp; beta; plaque formation and microglia-mediated neuroinflammation. The extracellular release of aggregated Tau is sensed by surveilling microglia through the involvement of various cell surface receptors. Among all, purinergic P2Y12R signaling is involved in microglial chemotaxis towards the damaged neurons. Microglial migration is highly linked with membrane-associated actin remodeling leading to the phagocytosis of extracellular Tau species. Here, we studied the formation of various actin structures such as podosome, lamellipodia and filopodia, in response to extracellular Tau monomers and aggregates. Microglial podosomes are colocalized with actin nucleator protein WASP, Arp2 and TKS5 adaptor protein during Tau-mediated migration. Moreover, the P2Y12 receptors were associated with F-actin-rich podosome structures, which signify the potential of Tau aggregates in microglial chemotaxis through the involvement of actin remodeling.</p>
10aAlzheimer `s disease10aFilopodia10amicroglia10aPodosome10aTau aggregates1 aChinnathambi, Subashchandrabose1 aDas, Rashmi1 aDesale, Smita, Eknath  uhttps://library.ncl.res.in/content/tau-aggregates-improve-purinergic-receptor-p2y12-associated-podosome-rearrangements