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-amyloid02896nas a2200229   4500008004100000022001400041245011200055210006900167260000900236300001400245490000700259520209400266653001102360653001702371653003402388653001302422653003002435653003502465100002302500700001502523856012802538       2025                        eng d  a1948-719300aDecoding the relationship between alzheimer's disease and type-2 diabetes via the protein aggregation prism0 aDecoding the relationship between alzheimers disease and type2 d  cAUG   a3003-30190 v163 a<p>
	Alzheimer's disease (AD) and type-2 diabetes (T2D) are two fatal human diseases and have been linked to the aberrant aggregation of two distinct peptides, amyloid-beta (A beta) and human islet amyloid polypeptide (hIAPP), respectively. These two peptide aggregates, even with distal deposition sites (brain and pancreas), act as mutual beneficiaries. We here unveiled the crosstalk in a self-consistent fashion using atomistic simulations by comparing the kinetics and thermodynamics of self- and cross-aggregations of A beta(42) and hIAPP and their modulations by preformed fibrillar templates. Templates (specifically hIAPP) generally accelerate aggregation, alter the relative order of aggregation rates (cross-aggregation &gt; A beta self-aggregation &gt; hIAPP self-aggregation for nontemplated and hIAPP self-aggregation &gt; cross-aggregation &gt; A beta self-aggregation for templated), and flip the mutual impact (hIAPP aggravates A beta aggregation in nontemplated and the reverse in templated). Higher instances of breaking larger aggregates and longer residence times of smaller aggregates decelerate aggregation, whereas interpeptide electrostatics (universal) and hydrogen bonds (templated) assist it. However, the equilibrium aggregability pattern contradicts kinetic rank-ordering, as A beta displays a higher aggregability than hIAPP, templates increase aggregability for both peptides, and A beta's self-aggregability supersedes cross-aggregability, which further surpasses hIAPP's self-aggregability. The equilibrium ensembles encompass polymorphic, nonfibrillar oligomers having substantially reduced alpha-helicity and slight beta-propensity, with both parallel and antiparallel interpeptide orientations, primarily stabilized by electrostatics. A higher equilibrium aggregability means a greater helix-breaking capacity, a bias toward parallel orientation, and a lesser structural polymorphism. Water expulsion from peptide surroundings and distortion of water tetrahedrality prove that aggregation follows the liquid-liquid phase separation (LLPS) model.</p>
10aamylin10aAmyloid-beta10aliquid-liquidphase separation10aOligomer10aself vs cross-aggregation10aunseeded vs seeded aggregation1 aTammara, Vaishnavi1 aDas, Atanu  uhttps://library.ncl.res.in/content/decoding-relationship-between-alzheimers-disease-and-type-2-diabetes-protein-aggregation