[{"_id":"project:2100","_type":"project","abstract":{"en":"50 mln people worldwide suffer dementia and 152 mln are projected by 2050, with Alzheimer’s (AD) as a primary cause. Despite decades of research, no therapies, slowing the disease progression or offering an efficient cure, are available. Preclinical trials failed to deliver treatment, due to a serious lack of understanding of both biomolecule interactions implicated in disease and how amyloid oligomers cause damage in the brain and thus can be targeted. We discovered the critical role of S100A9-driven amyloid-neuroinflammatory cascade in AD, Parkinson’s (PD) and traumatic brain Injury. Now we propose an integrated study of the molecular, cellular and tissue mechanisms of this cascade and how it modulates disease pathology. The mechanisms of hetero-assembly of proinflammatory S100A8/A9 into amyloid complexes with A? in AD and ?-synuclein in PD, if understood, provide insights into a key denominator of the origin of neurodegeneration (amyloid formation, the cytotoxicity effect and tissue damage). The S100A8/A9 driven self-assembly will be primarily targeted by therapeutic lead compounds to inhibit/reverse it. The diagnostic potential of S100A8/A9 amyloids will be explored. A breakthrough will be achieved by using a large array of advanced biophysical methods for in vitro to ex vivo studies, in which we have specific expertise: AFM, force tissue mapping, charged-detection mass-spectrometry, IR, NMR, fluorescence correlation spectroscopy, gamma-oscillation and others."},"project_id":"2019-01232_VR","identifier_short":"2019-01232","dates":{"start_date":"2020-01-01","end_date":"2022-12-31"},"organizations":[{"funding":[{"_id":2,"id":"202100-5208","sv":"Vetenskapsrådet","en":"Swedish Research Council"}]},{"coordinating":[{"_id":715,"id":"202100-2874","sv":"Umeå universitet","en":"Umeå University"}]}],"people":[{"project_leaders":[{"_id":"authority-person:62775","orcid":"0000-0001-5886-2023","name":"Morozova-Roche, Ludmilla","role":"principal_investigator","affiliation":[{"_id":715,"id":"202100-2874","sv":"Umeå universitet","en":"Umeå University"}]}]},{"other_personnel":[]}],"tags":[{"_id":11653,"id":"30103","sv":"Läkemedelskemi","en":"Medicinal Chemistry"},{"_id":11655,"id":"30105","sv":"Neurovetenskaper","en":"Neurosciences"},{"_id":11658,"id":"30108","sv":"Cell- och molekylärbiologi","en":"Cell and Molecular Biology"}],"titles":{"sv":"Orsakerna bakom neurodegeneration: Studier av sambanden mellan amyloida och neuro-inflammatoriska kaskader genom avancerade biofysiska metoder.","en":"Understanding the Origins of Neurodegeneration: Cross-Talk Between the Amyloid and Neuroinflammatory Cascades Studied by Advanced Biophysical Methods. "},"total_funding":"2400000","type_of_awards":{"sv":"Projektbidrag","en":"Project grant"},"publications":[],"links":[{"type":"pid","link":"https://su.diva-portal.org/smash/api/project/swecris/project:2100"}]}]