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Peer-reviewedCC BYBiomedicines

Alzheimer's Disease Neurofibrillary Pathophysiology: PTPRD- and Flavonol-Modified Mechanisms, Prevention and Therapeutics.

  • George R Uhl1,2,3
  • Joungil Choi4
  • Balaji Kannan1
  • Ian Henderson5
  • Emily Hess6
  • Hanna Rogers6
  • Darcy McFarland6
  • Hadley Dowell6
  • Sean Nolan6
  • Kevin Schultz6
6 affiliations
  1. 1Department of Neurology, School of Medicine, University of Maryland, 4A150a, VAMHCS, 10 N Greene St., Baltimore, MD 21201, USA.
  2. 2Department of Pharmacology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
  3. 3Neurology Service, VA Maryland Healthcare System, 10 N Greene St., Baltimore, MD 21201, USA.
  4. 4Research Service, VA Maryland Healthcare System, 10 N Greene St., Baltimore, MD 21201, USA.
  5. 5Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM 87106, USA.
  6. 6Department of Chemistry, Goucher College, Towson, MD 21204, USA.
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Abstract

A variety of evidence now supports two interrelated hypotheses concerning Alzheimer's disease (AD) neurofibrillary pathology (NFT), its prevention and treatment. The first hypothesis: the receptor type protein tyrosine phosphatase D (PTPRD) plays a key role in AD NFT pathogenesis by modulating activities of neuronal glycogen synthase kinase 3s (GSK3s) in hyperphosphorylating tau. The second hypothesis: positive allosteric modulation of PTPRD's downregulation of GSK3s by flavonols and improved flavonol analogs provides a novel path to prevention and treatment of AD. We review the convergence of evidence from human, mouse, in vitro and in silico studies that enhances the likely translational relevance of these hypotheses.

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Cite

BibTeXRIS
BibTeX
@article{uhl2026alzheimers,
  title = {{Alzheimer's Disease Neurofibrillary Pathophysiology: PTPRD- and Flavonol-Modified Mechanisms, Prevention and Therapeutics.}},
  author = {George R Uhl and Joungil Choi and Balaji Kannan and Ian Henderson and Emily Hess and Hanna Rogers and Darcy McFarland and Hadley Dowell and Sean Nolan and Kevin Schultz},
  journal = {Biomedicines},
  year = {2026},
  month = sep,
  doi = {10.3390/biomedicines14102210},
  url = {https://europepmc.org/article/MED/42940016},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Alzheimer's Disease Neurofibrillary Pathophysiology: PTPRD- and Flavonol-Modified Mechanisms, Prevention and Therapeutics.
AU  - George R Uhl
AU  - Joungil Choi
AU  - Balaji Kannan
AU  - Ian Henderson
AU  - Emily Hess
AU  - Hanna Rogers
AU  - Darcy McFarland
AU  - Hadley Dowell
AU  - Sean Nolan
AU  - Kevin Schultz
PY  - 2026
DA  - 2026/09/29
JO  - Biomedicines
DO  - 10.3390/biomedicines14102210
UR  - https://europepmc.org/article/MED/42940016
AB  - A variety of evidence now supports two interrelated hypotheses concerning Alzheimer's disease (AD) neurofibrillary pathology (NFT), its prevention and treatment. The first hypothesis: the receptor type protein tyrosine phosphatase D (PTPRD) plays a key role in AD NFT pathogenesis by modulating activities of neuronal glycogen synthase kinase 3s (GSK3s) in hyperphosphorylating tau. The second hypothesis: positive allosteric modulation of PTPRD's downregulation of GSK3s by flavonols and improved flavonol analogs provides a novel path to prevention and treatment of AD. We review the convergence of evidence from human, mouse, in vitro and in silico studies that enhances the likely translational relevance of these hypotheses.
SN  - 2227-9059
ER  -