Gamma secretase activating protein as profound target for Alzheimer's disease

Show simple item record Angira, Deekshi Thiruvenkatam, Vijay 2018-01-08T12:33:52Z 2018-01-08T12:33:52Z 2017-08
dc.identifier.citation Angira, Deekshi and Thiruvenkatam, Vijay, "Gamma secretase activating protein as profound target for Alzheimer's disease", Acta Crystallographica Section A, DOI: 10.1107/S2053273317083875, vol. 73, no. a2, pp. C1187, Aug. 2017.(Abstract) en_US
dc.identifier.issn 2053-2733
dc.description.abstract Alzheimer's disease is a form of progressive dementia followed by decline in cognitive abilities, neurological reflexes andlearning ability characterized by the presence of amyloid beta plaques and neurofibrillary tangles, their progression beingcomplemented by several cross talks between interconnected cell signaling pathways predominant in brain cells.Gamma Secretase Activating Protein (GSAP) involved in beta amyloid pathway is a 854 amino acid long protein (around 98kD) which is post translationally modified into an active 16kD protein with the help of regulators like Caspase 3 and 5Lipoxygenase at Caspase 3 processing domain present towards the C terminal at 737'DLD'739 position. In a sequentialproteolytic cleavage of APP and C-99 fragment by BACE-1 and ?-Secretase respectively, active GSAP is assumed to bring C-99 fragment and ?-secretase in close proximity by forming a ternary complex which leads to the production and depositionof A?40 and A?42 amyloid plaques. Through our work we target towards filling the voids that have been left unattended inthe field of GSAP, like its macromolecular structure determination through X-Ray crystallography or NMR, studying andexploring the other isoforms of GSAP to find out their structure and activity and to discern the role and action mechanism ofGSAP within the cell. Hence, we aim to clone and express GSAP in prokaryotic as well as in eukaryotic cells, in highly efficientex-pression vectors (such as pET19b, pET 32a, pMalc5X His, pcDNA 4) having different tags, and further to study thebinding efficiency of GSAP with potent inhibitors using X-ray crystallography. Along with GSAP isoform I, we also focus onGSAP isoform IV exploiting the fact that it has maximum similarity to canonical 16 kD GSAP isoform I. GSAP's role as anactivator of ?-amyloid production makes it a promising and ingenious therapeutic target for treatment of Alzheimer's diseasethus making it a prospective candidate to be probed for Alzheimer's cure and prevention.
dc.description.statementofresponsibility by Deekshi Angira and Vijay Thiruvenkatam
dc.format.extent vol. 73, no. a2, pp. C1187
dc.language.iso en en_US
dc.publisher International Union of Crystallography en_US
dc.subject Gamma Secretase Activating Protein en_US
dc.subject Beta amyloid pathway en_US
dc.subject Alzheimer's disease en_US
dc.title Gamma secretase activating protein as profound target for Alzheimer's disease en_US
dc.type Article en_US
dc.relation.journal Acta Crystallographica Section A

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