Please use this identifier to cite or link to this item: http://hdl.handle.net/10603/220240
Title: Studies on amyloid betamediated activation and novel signaling pathways in human platelets
Researcher: Sonkar Vijay Kumar
Guide(s): Dash Debabrata
Keywords: Life Sciences
University: Banaras Hindu University
Completed Date: 2014
Abstract: lzheimer s disease (AD) is characterized by neurotoxic Aand#946; plaque newlineformation in brain parenchyma and cerebral blood vessels known as newlinecerebral amyloid angiopathy (CAA). It is the most common cause of dementia in newlinethe elderly, affecting about 26 million people worldwide, and whose prevalence newlinehas been calculated to quadruple by 2050. Human platelets contain highest level newlineof Amyloid Precursor Protein (APP) among all the peripheral tissues (muscle, newlineepithelial, and circulating cells) contributing more than 90% of the circulating newlineAPP and these levels being comparable to the total APP levels in the brain. The newlinephysiological role of APP and its metabolites in platelets is not yet well newlineunderstood. Platelet APP is synthesized by the platelet precursor, the newlinemegakaryocyte, in the bone marrow rather than being the result of platelet newlineuptake of circulating APP. Platelets also express all the required enzymatic newlineactivities (and#945;, and#946; and and#947;and#8208;secretases) to produce all the APP metabolites (sAPPand#945;, newlinesAPPand#946; and Aand#946;), that are stored in intracellular granules. Proteolytic cleavage of newlineplatelet APP may occur both within intracellular organelles and on the platelet s newlinesurface. sAPPand#945; and Aand#946; peptides can be stored in and#945;and#8208;granules and released by newlineexocytosis upon platelet activation by thrombin or collagen, which induce Ca2+and#8208; newlinedependent degranulation. Platelet APP represents the major source of Aand#946; newlinedetected in whole blood. The main species of Aand#946; released from activated human newlineplatelet is Aand#946;1and#8208;40. Platelets also store and release neurotransmitters, such as newlineserotonin, glutamate and dopamine, and some neuronand#8208;related proteins such as newlineNand#8208;methyland#8208;dand#8208;aspartate, NMDA, receptors. Therefore, anucleated blood platelets newlineare considered as a key peripheral available model to study those metabolic newlinemechanisms, occurring in the central nervous system and related to AD.
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URI: http://hdl.handle.net/10603/220240
Appears in Departments:Department of Biochemistry

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