title: Bridging integrator 1 (BIN1): form, function, and Alzheimer's disease.
abstract: The bridging integrator 1 (BIN1) gene, also known as amphiphysin 2, has recently been identified as the most important risk locus for late onset Alzheimer's disease (LOAD), after apolipoprotein E (APOE). Here, we summarize the known functions of BIN1 and discuss the polymorphisms associated with LOAD, as well as their possible physiological effects. Emerging data suggest that BIN1 affects AD risk primarily by modulating tau pathology, but other affected cellular functions are discussed, including endocytosis/trafficking, inflammation, calcium homeostasis, and apoptosis. Epigenetic modifications are important for AD pathogenesis, and we review data that suggests the possible DNA methylation of the BIN1 promoter. Finally, given the potential contributions of BIN1 to AD pathogenesis, targeting BIN1 might present novel opportunities for AD therapy.
authors.affiliation: College of Medicine and Pharmaceutics, Ocean University of China, Qingdao 266003, China; Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao 266071, China.
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D006801:Humans; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024801:Tauopathies / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; C075637:amphiphysin
keywords: Alzheimer's disease; BIN1; genetics; pathogenesis; tau; therapy