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@ARTICLE{Saeed:285249,
      author       = {Saeed, Sania and Khan, Shahrukh and Noor, Aneeqa and Zerr,
                      Inga and Zafar, Saima},
      title        = {{T}herapeutic {P}otential of {A}myloid-β {I}nteractors in
                      {R}apidly {P}rogressive {A}lzheimer's {D}isease-{A}n {I}n
                      {S}ilico {S}tudy.},
      journal      = {Molecular informatics},
      volume       = {45},
      number       = {2},
      issn         = {1868-1743},
      address      = {Weinheim},
      publisher    = {Wiley-VCH-Verl.},
      reportid     = {DZNE-2026-00191},
      pages        = {e70024},
      year         = {2026},
      abstract     = {Rapidly progressive Alzheimer's disease (rpAD) is a rare
                      but severe form of Alzheimer's disease characterized by
                      accelerated cognitive decline and limited therapeutic
                      options. Conventional anti-amyloid-β interventions have
                      shown little success due to poor target specificity,
                      neurotoxicity, and lack of efficacy, underscoring the need
                      for novel therapeutic strategies. This study aimed to
                      identify and prioritize molecular targets associated with
                      rpAD by investigating the protein interactome of amyloid-β
                      (Aβ42) using integrative computational approaches.
                      Functional enrichment, protein-protein interaction network
                      analysis, and community clustering revealed that
                      rpAD-specific Aβ42 interactors were predominantly involved
                      in mitochondrial bioenergetics, redox regulation, and
                      cytoskeletal stability, pathways central to neuronal
                      survival and synaptic function. Molecular docking identified
                      fumarate hydratase, carbonyl reductase 1, and the F-actin
                      capping protein as high-affinity interactors of Aβ42,
                      linking these proteins to energy failure, oxidative stress,
                      and synaptic dysfunction. Virtual screening of a therapeutic
                      drug library against fumarate hydratase identified several
                      compounds with strong binding affinities, among which
                      quinestrol, estradiol benzoate, norethindrone, tamibarotene,
                      drospirenone, and ketanserin emerged as lead candidates.
                      Pharmacokinetic profiling, including ADMET modeling,
                      confirmed their blood-brain barrier permeability and
                      drug-likeness, supporting their potential as central nervous
                      system active agents. Together, this work highlights key
                      molecular targets in rpAD and proposes repurposed,
                      pharmacologically diverse compounds with multitarget
                      neuroprotective potential. By utilizing in silico analysis,
                      the study provides a rational framework for target discovery
                      and drug prioritization in rpAD, offering a foundation for
                      future experimental validation and the development of
                      translational research.},
      keywords     = {Alzheimer Disease: drug therapy / Alzheimer Disease:
                      metabolism / Amyloid beta-Peptides: metabolism / Amyloid
                      beta-Peptides: chemistry / Humans / Molecular Docking
                      Simulation / Computer Simulation / Protein Interaction Maps
                      / Aβ interactors (Other) / molecular docking (Other) /
                      pharmacokinetics (Other) / rapidly progressive Alzheimer's
                      disease (Other) / rpAD (Other) / virtual screening (Other) /
                      Amyloid beta-Peptides (NLM Chemicals)},
      cin          = {AG Zerr},
      ddc          = {530},
      cid          = {I:(DE-2719)1440011-1},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41692408},
      doi          = {10.1002/minf.70024},
      url          = {https://pub.dzne.de/record/285249},
}