» Articles » PMID: 19794442

Advances in Tau-focused Drug Discovery for Alzheimer's Disease and Related Tauopathies

Overview
Specialty Pharmacology
Date 2009 Oct 2
PMID 19794442
Citations 187
Authors
Affiliations
Soon will be listed here.
Abstract

Neuronal inclusions comprised of the microtubule-associated protein tau are found in numerous neurodegenerative diseases, commonly known as tauopathies. In Alzheimer's disease - the most prevalent tauopathy - misfolded tau is probably a key pathological agent. The recent failure of amyloid-beta-targeted therapeutics in Phase III clinical trials suggests that it is timely and prudent to consider alternative drug discovery strategies for Alzheimer's disease. Here, we focus on strategies directed at reducing misfolded tau and compensating for the loss of normal tau function.

Citing Articles

Designed Cell-Penetrating Peptide Constructs for Inhibition of Pathogenic Protein Self-Assembly.

Kalmouni M, Oh Y, Alata W, Magzoub M Pharmaceutics. 2024; 16(11).

PMID: 39598566 PMC: 11597747. DOI: 10.3390/pharmaceutics16111443.


CYR61 Acts as an Intracellular Microtubule-Associated Protein and Coordinates Mitotic Progression via PLK1-FBW7 Pathway.

Hu K, Xie L, Wu W, Zhang J, Li Y, He J Int J Biol Sci. 2024; 20(8):3140-3155.

PMID: 38904029 PMC: 11186368. DOI: 10.7150/ijbs.93335.


A small-molecule microtubule-stabilizing agent safely reduces Aβ plaque and tau pathology in transgenic mouse models of Alzheimer's disease.

Yao Y, Muench M, Alle T, Zhang B, Lucero B, Perez-Tremble R Alzheimers Dement. 2024; 20(7):4540-4558.

PMID: 38884283 PMC: 11247666. DOI: 10.1002/alz.13875.


Recent Advances in Targeting Transition Metals (Copper, Iron, and Zinc) in Alzheimer's Disease.

Singh R, Panghal A, Jadhav K, Thakur A, Verma R, Singh C Mol Neurobiol. 2024; 61(12):10916-10940.

PMID: 38809370 DOI: 10.1007/s12035-024-04256-8.


Liquid-liquid phase separation in Alzheimer's disease.

Fu Q, Zhang B, Chen X, Chu L J Mol Med (Berl). 2024; 102(2):167-181.

PMID: 38167731 DOI: 10.1007/s00109-023-02407-3.


References
1.
Berger Z, Ravikumar B, Menzies F, Oroz L, Underwood B, Pangalos M . Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum Mol Genet. 2005; 15(3):433-42. DOI: 10.1093/hmg/ddi458. View

2.
Cruz J, Kim D, Moy L, Dobbin M, Sun X, Bronson R . p25/cyclin-dependent kinase 5 induces production and intraneuronal accumulation of amyloid beta in vivo. J Neurosci. 2006; 26(41):10536-41. PMC: 6674706. DOI: 10.1523/JNEUROSCI.3133-06.2006. View

3.
Liu F, Iqbal K, Grundke-Iqbal I, Hart G, Gong C . O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer's disease. Proc Natl Acad Sci U S A. 2004; 101(29):10804-9. PMC: 490015. DOI: 10.1073/pnas.0400348101. View

4.
Noble W, Olm V, Takata K, Casey E, Mary O, Meyerson J . Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron. 2003; 38(4):555-65. DOI: 10.1016/s0896-6273(03)00259-9. View

5.
Hampel H, Ewers M, Burger K, Annas P, Mortberg A, Bogstedt A . Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry. 2009; 70(6):922-31. View