title: [New biomarkers and drug targets for diagnosis and therapy of Alzheimer's disease (molecular determinants of zinc-dependent oligomerization of Β-amyloid)].
abstract: In view of the amyloid hypothesis of Alzheimer's disease (AD), the key molecular event is the structural transition of Β-amyloid from the physiologically normal monomer state to soluble neurotoxic oligomers accumulating in the form of insoluble extracellular aggregates (amyloid plaques) in brain tissues. Zinc ions are known to play a crucial role in the formation of these pathological aggregates. The authors and collaborators have identified that the certain chemical modification and point amino acid substitutions in the metal-binding domain play a critical role in the formation of neurotoxic zinc-dependent oligomers and induce the development of cerebral amyloidosis and other pathological processes characteristic of AD. The results allow to use these forms of Β-amyloid as potential biomarkers of early diagnosis of AD. Zinc-dependent dimerization and oligomerization of Β-amyloid can be used as drug target for treatment of AD.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow.
authors.forename: S A
authors.initials: SA
authors.lastname: Kozin
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow.
authors.forename: A A
authors.initials: AA
authors.lastname: Makarov
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D055503:Protein Multimerization; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D015032:Zinc