Related Experiment Video
Updated: May 13, 2026
09:22
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Progress and developments in tau aggregation inhibitors for Alzheimer disease
Bruno Bulic1, Marcus Pickhardt, Eckhard Mandelkow
1Laboratory of Organic Synthesis of Functional Systems, Humboldt-Universität zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin, Germany. bruno.bulic@huberlin.de
Journal of Medicinal Chemistry
|March 15, 2013
Summary
Researchers are developing small molecule tau aggregation inhibitors (TAGIs) for Alzheimer disease. These compounds show promise in clinical trials, with emerging structure-activity relationships suggesting successful translation to the clinic.
Area of Science:
- Neuroscience
- Pharmacology
- Medicinal Chemistry
Background:
- Alzheimer disease (AD) research is exploring diverse pharmacological targets.
- The microtubule-associated protein tau is a key target due to its central role in neurodegeneration.
Purpose of the Study:
- To review the development of nonpeptidic small molecule tau aggregation inhibitors (TAGIs).
- To summarize the advancement of TAGIs toward clinical trials.
Main Methods:
- Classification of TAGIs based on chemical structures.
- Analysis of structure-activity relationships and binding modes.
- Review of recent medicinal chemistry efforts and in vivo data.
Main Results:
- Emerging structure-activity traits and specific hydrogen bonding interactions identified for TAGIs.
- Encouraging in vivo data supporting the therapeutic potential of TAGIs.
Conclusions:
- Nonpeptidic small molecule TAGIs represent a promising therapeutic strategy for Alzheimer disease.
- Continued medicinal chemistry efforts and positive preclinical data suggest successful clinical translation.
Related Concept Videos
01:22Alzheimer's Disease: Treatment
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
01:26Alzheimer's Disease: Overview
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
01:23Alzheimer Disease ll: Pathophysiology
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
01:29Alzheimer Disease l: Introduction
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
01:22Dementia l: Introduction
Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...