{"id":"https://openalex.org/G251617455","display_name":"Validating a Novel Lipid Phosphatase Target in Alzheimer's Disease","description":"PUBLIC HEALTH RELEVANCE: Alzheimer's disease is characterized clinically by memory impairment and pathologically by the deposition of amyloid-2 peptide (A2) in the brains of AD patients. Evidence is accumulating which supports the hypothesis that A2 may be a factor in early neuronal dysfunction associated with AD. Specifically, levels of A2 correlate with disease progression in animal models of AD. In the brain, A2 interferes with normal neuronal function by mechanisms that are not yet fully understood. We have recently published data indicating that a specific lipid, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], which regulates key aspects of neural function, is altered after treatment of neurons with A2. Additionally, mice with low levels of a specific lipid phosphatase, synaptojanin 1 (Synj1), responsible for metabolizing PI(4,5)P2, are resistant to A2-induced neuronal dysfunction. We propose to further investigate the role Synj1 in A2-induced neuronal dysfunction by using mutants of Synj1 to probe its function in neurons lacking endogenous Synj1. Additionally, we propose to cross a mouse model of AD with mice lacking one copy of Synj1. Since this genotype was protective in vitro, we expect these mice to have ameliorated AD-associated behavioral deficits in learning and memory tasks. Completion of these studies will determine if Synj1 can be a valid target for future AD therapeutic strategies.","funder_award_id":"R01NS074536","funder":{"id":"https://openalex.org/F4320337359","display_name":"National Institute of Neurological Disorders and Stroke","doi":"10.13039/100000065"},"funded_outputs":["https://openalex.org/W1982959887","https://openalex.org/W1990997484","https://openalex.org/W2049353782","https://openalex.org/W2051583809","https://openalex.org/W2064370541","https://openalex.org/W2072826181","https://openalex.org/W2104447725","https://openalex.org/W2146778032","https://openalex.org/W2550804112"],"funded_outputs_count":9,"parent_awards":[],"sub_awards":[],"sub_awards_count":0,"amount":null,"currency":"USD","amount_usd":null,"amount_usd_basis":null,"recipients":[],"recipient_countries":[],"recipient_regions":[],"research_scope":{"is_research":true,"basis":"funder_default","tier":1},"funding_type":"research","funder_scheme":"R01","start_date":"2011-01-15","end_date":"2015-12-31","start_year":2011,"end_year":2015,"landing_page_url":"https://reporter.nih.gov/project-details/8212249","doi":null,"provenance":"nih_exporter","lead_investigator":{"given_name":"TAE-WAN","family_name":"KIM","orcid":null,"role_start":null,"affiliation":{"name":"COLUMBIA UNIVERSITY HEALTH SCIENCES","country":"UNITED STATES","ids":null}},"co_lead_investigator":null,"investigators":null,"works_api_url":"https://api.openalex.org/works?filter=awards.id:G251617455","primary_topic":{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":0.9,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":0.9,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"institution_awarded":[{"id":"https://openalex.org/I2800649613","display_name":"University of Missouri Health System","ror":"https://ror.org/03yp8z857","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2800649613"]},{"id":"https://openalex.org/I78577930","display_name":"Columbia University","ror":"https://ror.org/00hj8s172","country_code":"US","type":"education","lineage":["https://openalex.org/I78577930"]}],"updated_date":"2026-10-16T03:01:01.000Z","created_date":"2026-10-09T19:56:01.000Z"}