Related Experiment Video
Updated: Jul 5, 2026
12:55
Assay for Phosphorylation and Microtubule Binding Along with Localization of Tau Protein in Colorectal Cancer Cells
Published on: October 10, 2017
Decrease of protein phosphatase 2A and its association with accumulation and hyperphosphorylation of tau in Down
Zhihou Liang1, Fei Liu, Khalid Iqbal
1Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314-6399, USA.
Journal of Alzheimer'S Disease : JAD
|April 24, 2008
Summary
Individuals with Down syndrome (DS) show decreased protein phosphatase 2A (PP2A) levels, leading to abnormal tau protein hyperphosphorylation and accumulation, a hallmark of Alzheimer's disease (AD). This suggests PP2A down-regulation is involved in AD pathology in DS.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Down syndrome (DS) is characterized by the early development of neurofibrillary tangles, a key lesion in Alzheimer's disease (AD).
- Tau protein hyperphosphorylation is implicated in neurofibrillary tangle formation in AD.
- The role of protein phosphatase 2A (PP2A) in tau pathology in DS was previously unclear.
Purpose of the Study:
- To investigate the levels and activity of tau phosphatases in the brain of individuals with Down syndrome.
- To determine the relationship between PP2A levels and tau hyperphosphorylation in DS.
Main Methods:
- Quantitative Western blot analysis was employed to measure the levels of various tau phosphatases, including PP2A, PP1, PP2B, and PP5.
- Specific antibodies were used to detect tau phosphorylation at multiple abnormal sites.
Main Results:
- A significant decrease in the catalytic subunit of PP2A was observed in DS brain tissue.
- No significant changes were found in the levels of PP1, PP2B, or PP5.
- Decreased PP2A levels correlated negatively with total tau levels and tau phosphorylation at sites like Ser199, Thr205, Thr212, Ser262, Ser396, and Ser422.
Conclusions:
- Protein phosphatase 2A (PP2A) is down-regulated in the brain of individuals with Down syndrome.
- This down-regulation of PP2A may contribute to the abnormal hyperphosphorylation and accumulation of tau protein, potentially driving Alzheimer's disease pathology in DS.
Related Concept Videos
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...
01:02Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
01:24Parkinson Disease ll: Pathophysiology
Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
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...
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
01:21Huntington Disease l: Introduction
Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...