{"id":{"repo_id":"purdue-thes","oai_identifier":"oai:docs.lib.purdue.edu:open_access_dissertations-2628"},"canonical_url":"https://search.dev.ndltd.org/etd/purdue-thes/oai:docs.lib.purdue.edu:open_access_dissertations-2628","repository":{"repo_id":"purdue-thes","name":"Purdue University","base_url":"https://docs.lib.purdue.edu/do/oai/"},"display":{"title":"STRESS GRANULES MODULATE SYK TO CAUSE MICROGLIAL DYSFUNCTION IN ALZHEIMER’S DISEASE","abstract":"Microglial cells in the brains of Alzheimer’s patients are recruited to amyloid beta (Aβ) plaques and exhibit an activated phenotype, but are defective for plaque removal by phagocytosis. To explore the molecular basis for these phenomena, I hypothesized that defects in the functions of the protein-tyrosine kinase SYK, which is important both for macrophage activation and phagocytosis, might underlie much of this pathology. Recent evidence from our lab indicates that SYK can associate with stress granules, ribonucleoprotein particles that form in stressed cells and contain inactive translation initiation complexes. I found that microglial cell lines and primary mouse brain microglia, when stressed by exposure to sodium arsenite or Aβ(1-42) peptides or fibrils, form extensive stress granules to which the tyrosine kinase, SYK, is recruited. SYK enhances the formation of stress granules as evidenced by the inhibition of stress granule formation by small molecule inhibitors, knockdown of SYK expression by shRNA and SYK haploinsufficiency in mouse microglial cells. SYK is active within the resulting stress granules where it catalyzes the phosphorylation of stress granule-associated proteins on tyrosine. SYK-dependent stress granule","abstract_html":"Microglial cells in the brains of Alzheimer’s patients are recruited to amyloid beta (Aβ) plaques and exhibit an activated phenotype, but are defective for plaque removal by phagocytosis. To explore the molecular basis for these phenomena, I hypothesized that defects in the functions of the protein-tyrosine kinase SYK, which is important both for macrophage activation and phagocytosis, might underlie much of this pathology. Recent evidence from our lab indicates that SYK can associate with stress granules, ribonucleoprotein particles that form in stressed cells and contain inactive translation initiation complexes. I found that microglial cell lines and primary mouse brain microglia, when stressed by exposure to sodium arsenite or Aβ(1-42) peptides or fibrils, form extensive stress granules to which the tyrosine kinase, SYK, is recruited. SYK enhances the formation of stress granules as evidenced by the inhibition of stress granule formation by small molecule inhibitors, knockdown of SYK expression by shRNA and SYK haploinsufficiency in mouse microglial cells. SYK is active within the resulting stress granules where it catalyzes the phosphorylation of stress granule-associated proteins on tyrosine. SYK-dependent stress granule","abstract_has_math":false,"creators":["Ghosh, Soumitra"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"PULSe","degree_department":null,"school":null,"contributors":["Robert L Geahlen","Riyi Shi","Jean Christophe Rochet","Val J Watts"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-01-01T08:00:00Z","date_published":"2015-01-01T08:00:00Z","updated_at":"2026-07-24T03:54:44Z","subjects":["Alzheimer's disease","microglia","Spleen tyrosine kinase (SYK)","stress granules"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://docs.lib.purdue.edu/open_access_dissertations/1412","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Robert L Geahlen","Riyi Shi","Jean Christophe Rochet","Val J Watts"]},{"key":"dc:creator","label":"Author","values":["Ghosh, Soumitra"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["PULSe"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Alzheimer's disease","microglia","Spleen tyrosine kinase (SYK)","stress granules"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://docs.lib.purdue.edu/open_access_dissertations/1412"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Microglial cells in the brains of Alzheimer’s patients are recruited to amyloid beta (Aβ) plaques and exhibit an activated phenotype, but are defective for plaque removal by phagocytosis. To explore the molecular basis for these phenomena, I hypothesized that defects in the functions of the protein-tyrosine kinase SYK, which is important both for macrophage activation and phagocytosis, might underlie much of this pathology. Recent evidence from our lab indicates that SYK can associate with stress granules, ribonucleoprotein particles that form in stressed cells and contain inactive translation initiation complexes. I found that microglial cell lines and primary mouse brain microglia, when stressed by exposure to sodium arsenite or Aβ(1-42) peptides or fibrils, form extensive stress granules to which the tyrosine kinase, SYK, is recruited. SYK enhances the formation of stress granules as evidenced by the inhibition of stress granule formation by small molecule inhibitors, knockdown of SYK expression by shRNA and SYK haploinsufficiency in mouse microglial cells. SYK is active within the resulting stress granules where it catalyzes the phosphorylation of stress granule-associated proteins on tyrosine. SYK-dependent stress granule"]},{"key":"dc:title","label":"Title","values":["STRESS GRANULES MODULATE SYK TO CAUSE MICROGLIAL DYSFUNCTION IN ALZHEIMER’S DISEASE"]}]}],"canonical_facts":{"dc:contributor":["Robert L Geahlen","Riyi Shi","Jean Christophe Rochet","Val J Watts"],"dc:creator":["Ghosh, Soumitra"],"dc:description.abstract":["Microglial cells in the brains of Alzheimer’s patients are recruited to amyloid beta (Aβ) plaques and exhibit an activated phenotype, but are defective for plaque removal by phagocytosis. To explore the molecular basis for these phenomena, I hypothesized that defects in the functions of the protein-tyrosine kinase SYK, which is important both for macrophage activation and phagocytosis, might underlie much of this pathology. Recent evidence from our lab indicates that SYK can associate with stress granules, ribonucleoprotein particles that form in stressed cells and contain inactive translation initiation complexes. I found that microglial cell lines and primary mouse brain microglia, when stressed by exposure to sodium arsenite or Aβ(1-42) peptides or fibrils, form extensive stress granules to which the tyrosine kinase, SYK, is recruited. SYK enhances the formation of stress granules as evidenced by the inhibition of stress granule formation by small molecule inhibitors, knockdown of SYK expression by shRNA and SYK haploinsufficiency in mouse microglial cells. SYK is active within the resulting stress granules where it catalyzes the phosphorylation of stress granule-associated proteins on tyrosine. SYK-dependent stress granule"],"dc:identifier":["https://docs.lib.purdue.edu/open_access_dissertations/1412"],"dc:subject":["Alzheimer's disease","microglia","Spleen tyrosine kinase (SYK)","stress granules"],"dc:title":["STRESS GRANULES MODULATE SYK TO CAUSE MICROGLIAL DYSFUNCTION IN ALZHEIMER’S DISEASE"],"thesis:degree_discipline":["PULSe"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T03:54:44Z"}