Explore the latest discoveries in memory loss research.
Dive into our collection of groundbreaking studies, insightful papers, essential resources, and our newest advancements in the field of memory loss.
Blocking Site-Specific Cleavage of Human Tau Delays Progression of Disease-Related Phenotypes in Genetically Matched Tau-Transgenic Mice Modeling Frontotemporal Dementia
Steuer EL, Kemper LJ, Hlynialuk CJW, Leinonen-Wright K, Montonye ML, Lapcinski IP, Forster CL, Ashe KH, Liu P.
Blocking Site-Specific Cleavage of Human Tau Delays Progression of Disease-Related Phenotypes in Genetically Matched Tau-Transgenic Mice Modeling Frontotemporal Dementia.
Journal of Neuroscience. 2022;42(23):4737-4754.
PMID: 35508385. DOI: 10.1523/JNEUROSCI.0543-22.2022.
A Soluble Tau Fragment Generated by Caspase-2 Is Associated with Dementia in Lewy Body Disease
Smith BR, Nelson KM, Kemper LJ, Leinonen-Wright K, Petersen A, Keene CD, Ashe KH.
A Soluble Tau Fragment Generated by Caspase-2 Is Associated with Dementia in Lewy Body Disease.
Acta Neuropathologica Communications. 2019;7:1-9.
PMID: 31362787. DOI: 10.1186/s40478-019-0765-8.
Reviews & Perspectives
Walters, M.A., Pockes, S., Ashe, K.H. (2026).
Targeting Caspase-2 for the Treatment of Dementia.
Wolfe, M.S. (eds) Advances in Drug Discovery for Alzheimer’s Disease. Topics in Medicinal Chemistry, vol 44. Springer, Cham.
Liu P, Ashe KH.
The Molecular Implications of a Caspase-2-Mediated Site-Specific Tau Cleavage in Tauopathies.
Neural Regeneration Research. 2021;16(9):1774-1775.
PMID: 33510072. DOI: https://doi.org/10.4103/1673-5374.306073
Pockes S, Walters MA, Ashe KH.
Targeting Caspase-2 Interactions with Tau in Alzheimer's Disease and Related Dementias.
Translational Research. 2023;254:34-40.
PMID: 36328077. DOI: 10.1016/j.trsl.2022.10.009.
Target Discovery
Hoover BR, Reed MN, Su JJ, Penrod RD, Kotilinek LA, Grant MK, Pitstick R, Carlson GA, Lanier LM, Yuan LL, Ashe KH, Liao DZ.
Tau Mislocalization to Dendritic Spines Mediates Synaptic Dysfunction Independently of Neurodegeneration.
Neuron. 2010;68(6):1067-1081.
PMID: 21172610. DOI: 10.1016/j.neuron.2010.11.030.
Zhao X, Kotilinek LA, Smith B, Hlynialuk C, Zahs K, Ramsden M, Cleary J, Ashe KH.
Caspase-2 Cleavage of Tau Reversibly Impairs Memory.
Nature Medicine. 2016;22(11):1268-1276.
PMID: 27723722. DOI: 10.1038/nm.4199.
Teravskis PJ, Oxnard BR, Miller EC, Kemper L, Ashe KH, Liao D.
Phosphorylation in Two Discrete Tau Domains Regulates a Stepwise Process Leading to Postsynaptic Dysfunction.
Journal of Physiology. 2019;597:2483-2498.
PMID: 30714637. DOI: 10.1113/JP277696.
Singh G, Liu P, Yao KR, Strasser JM, Hlynialuk C, Leinonen-Wright K, Teravskis PJ, Choquette JM, Ikramuddin J, Bresinsky M, Nelson KM, Liao D, Ashe KH, Walters MA, Pockes S.
Caspase-2 Inhibitor Blocks Tau Truncation and Restores Excitatory Neurotransmission in Neurons Modeling FTDP-17 Tauopathy.
ACS Chemical Neuroscience. 2022;13(10):1549-1557.
PMID: 35522720. DOI: 10.1021/acschemneuro.2c00100.
Human Biomarkers
Liu P, Smith BR, Huang ES, Mahesh A, Vonsattel JPG, Petersen AJ, Gomez-Pastor R, Ashe KH.
A Soluble Truncated Tau Species Related to Cognitive Dysfunction and Caspase-2 Is Elevated in the Brain of Huntington's Disease Patients.
Acta Neuropathologica Communications. 2019;7:1-13.
PMID: 31358058. DOI: 10.1186/s40478-019-0764-9.
Liu P, Smith BR, Montonye ML, Higgins L, Guerrero CR, Markowski TW, Zhao X, Petersen AJ, Knopman DS, Petersen RC, Ashe KH.
A Soluble Truncated Tau Species Related to Cognitive Dysfunction Is Elevated in the Brain of Cognitively Impaired Human Individuals.
Scientific Reports. 2020;10:3869.
PMID: 32123248. DOI: 10.1038/s41598-020-60777-x.
Hlynialuk C, Kemper L, Leinonen-Wright K, Petersen RC, Ashe KH, Smith BR.
Caspase-2 mRNA Levels Are Not Elevated in Mild Cognitive Impairment, Alzheimer's Disease, Huntington's Disease, or Lewy Body Dementia.
PLoS One. 2022;17(9):e0274784.
PMID: 36197950. DOI: 10.1371/journal.pone.0274784.
Therapeutic Discovery & Development
Bresinsky M, Strasser JM, Vallaster B, Liu P, McCue WM, Fuller J, Hubmann A, Singh G, Nelson KM, Cuellar ME, Wilmot CM, Finzel BC, Ashe KH, Walters MA, Pockes S.
Structure-Based Design and Biological Evaluation of Novel Caspase-2 Inhibitors Based on the Peptide AcVDVAD-CHO and the Caspase-2-Mediated Tau Cleavage Sequence YKPVD314.
ACS Pharmacology & Translational Science. 2022;5(1):20-40.
PMID: 35059567. DOI: 10.1021/acsptsci.1c00251.
Bresinsky M, Strasser JM, Hubmann A, Vallaster B, McCue WM, Fuller J, Singh G, Nelson KM, Cuellar ME, Finzel BC, Ashe KH, Walters MA, Pockes S.
Characterization of Caspase-2 Inhibitors Based on Specific Sites of Caspase-2-Mediated Proteolysis.
Archiv der Pharmazie. 2022;355(9):e2200095.
PMID: 35642311. DOI: 10.1002/ardp.202200095.
Cuellar ME, Yang M, Karavadhi S, Zhang YQ, Zhu H, Sun H, Shen M, Hall MD, Patnaik S, Ashe KH, Walters MA, Pockes S.
An Electrophilic Fragment Screening for the Development of Small Molecules Targeting Caspase-2.
European Journal of Medicinal Chemistry. 2023;259:115632.
PMID: 37541771. DOI: 10.1016/j.ejmech.2023.115632.
Fuller JL, Shi K, Pockes S, Finzel BC, Ashe KH, Walters MA.
Reengineering of Circularly Permuted Caspase-2 to Enhance Enzyme Stability and Enable Crystallographic Studies.
ACS Chemical Biology. 2025;20(4):845-857.
PMID: 40117490. DOI: 10.1021/acschembio.4c00795.