Related Experiment Video
Updated: Jul 28, 2025
11:04
Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast
Published on: June 23, 2018
7.4K
Protein aggregation: Consequences, mechanism, characterization and inhibitory strategies
Nabeela Majid1, Rizwan Hasan Khan1
1Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
International Journal of Biological Macromolecules
|June 3, 2023
Summary
Protein misfolding and aggregation cause neurodegenerative diseases like Alzheimer's and Parkinson's. Current treatments are symptomatic, highlighting the need for therapies targeting the root cause of protein aggregation.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Proteins are vital for cellular functions but can misfold and aggregate under altered environmental conditions.
- Protein aggregation overwhelms cellular quality control systems (ubiquitin-proteasomal machinery and autophagy), leading to toxicity.
- Misfolded proteins like amyloid-beta and alpha-synuclein are implicated in diseases such as Alzheimer's and Parkinson's.
Purpose of the Study:
- To review the fundamental mechanisms of protein misfolding and aggregation.
- To discuss current therapeutic strategies and identify gaps in treating protein misfolding diseases.
- To provide a comprehensive resource for researchers in neuroscience and related fields.
Main Methods:
- Literature review of protein misfolding and aggregation.
- Analysis of cellular quality control pathways.
- Examination of disease-associated protein aggregation mechanisms.
- Survey of existing and hypothetical therapeutic interventions.
Main Results:
- Protein misfolding and aggregation are central to the pathogenesis of major neurodegenerative diseases.
- Existing treatments offer symptomatic relief but do not address the underlying cause of protein aggregation.
- A critical need exists for novel therapeutics targeting the initiation of protein aggregation.
Conclusions:
- Understanding protein misfolding and aggregation is crucial for developing effective disease-modifying therapies.
- Targeting the initial steps of protein aggregation holds promise for treating neurodegenerative disorders.
- This review consolidates knowledge to guide future research in developing causative treatments for proteinopathies.
Keywords:
Aggregation prone regionConfocal laser scanning microscopyPreformed fibrilsProtein misfoldingSecondary nucleationZetasizerMore Related Videos
Related Concept Videos
03:03Amyloid Fibrils
9.6K
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,...
9.6K
02:04Protein-protein Interfaces
12.6K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.6K
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
1.9K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
1.9K
01:29Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
608
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
608
03:00Molecular Chaperones and Protein Folding
18.1K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
18.1K
01:13The Proteasome
914
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
914