Related Experiment Video
Updated: Jan 22, 2026
10:08
Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
Published on: August 28, 2012
12.2K
Activated PPARγ Abrogates Misprocessing of Amyloid Precursor Protein, Tau Missorting and Synaptotoxicity
Susanne Moosecker1, Patrícia Gomes2,3, Chrysoula Dioli2,3
1Department Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
Frontiers in Cellular Neuroscience
|July 3, 2019
Summary
Pioglitazone (Pio) may protect against Alzheimer's disease (AD) by preventing synaptic damage. This drug targets pathways involved in amyloid-beta processing and tau pathology, offering potential for AD treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Endocrinology
Background:
- Type 2 diabetes is a risk factor for dementia, including Alzheimer's disease (AD).
- Pioglitazone (Pio), a PPARγ agonist, improves insulin sensitivity and shows potential for AD symptom management via unknown mechanisms.
- Synaptic malfunction and loss contribute to cognitive deficits in AD.
Purpose of the Study:
- To investigate how Pioglitazone (Pio) counters synaptic malfunction and loss in Alzheimer's disease (AD) pathology.
- To elucidate the mechanisms underlying Pio's potential therapeutic effects in AD.
Main Methods:
- Experiments were conducted on primary mouse neuronal cultures and a human neural cell line (SH-SY5Y).
- Assessed the impact of Pio on amyloid-beta (Aβ) processing, tau pathology, and synaptic markers.
- Utilized GW9662, a selective PPARγ inhibitor, to determine the role of PPARγ mediation.
Main Results:
- Pio treatment attenuated Aβ-triggered amyloid precursor protein (APP) misprocessing.
- Pio inhibited Aβ-induced tau accumulation, hyperphosphorylation, and synaptic missorting.
- Pio prevented Aβ-induced loss of PSD95-positive synapses, a mechanism mediated by PPARγ.
Conclusions:
- Activated PPARγ protects neurons against APP misprocessing, tau hyperphosphorylation, and synaptic loss.
- Pio's mechanism involves preventing tau missorting to synapses and subsequent synaptic damage.
- These findings support further research into PPARγ agonists for preventing and treating synaptic pathology in AD.
Related Concept Videos
03:03Amyloid Fibrils
11.7K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
11.7K
03:03Amyloid Fibrils
6.4K
6.4K
01:39Mitochondrial Precursor Proteins
3.6K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
3.6K
01:16Kendall's Tau Test
1.1K
Kendall's tau test, also known as the Kendall rank coefficient test, is a nonparametric method for assessing association between two variables. This test is particularly useful for identifying significant correlations when the distributions of the sample and population are unknown. Developed in 1938 by the British statistician Sir Maurice George Kendall, the tau coefficient (denoted as τ) serves as a rank correlation coefficient, with values ranging from -1 to +1.
A τ value of +1 indicates...
A τ value of +1 indicates...
1.1K
01:22Activation and Inactivation of G Proteins
11.2K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
11.2K
02:50Conjugated Proteins
27.5K
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
27.5K