Related Experiment Video
Updated: Jul 28, 2026
09:35
Enrichment of Detergent-insoluble Protein Aggregates from Human Postmortem Brain
Published on: October 24, 2017
Protein aggregation and neurodegenerative disease
Christopher A Ross1, Michelle A Poirier
1Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Ross Research Building, Room 618, 720 Rutland Avenue, Baltimore, Maryland 21205, USA. caross@jhu.edu
Nature Medicine
|July 24, 2004
Summary
Neurodegenerative diseases share common mechanisms like protein aggregation. Understanding early steps in these pathways is key to developing effective treatments for conditions such as Alzheimer
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Neurodegenerative diseases (Alzheimer's, Parkinson's, Huntington's, ALS, prion diseases) share common cellular and molecular mechanisms.
- Protein aggregation, forming amyloid fibers from misfolded proteins, is a hallmark of these conditions.
- The overlap between protein deposition and cell degeneration suggests inclusions are end-stage events in a pathogenic cascade.
Purpose of the Study:
- To explore common pathogenic pathways in neurodegenerative diseases.
- To investigate the role of protein aggregation and cellular toxicity.
- To identify potential targets for rational therapeutic development.
Main Methods:
- Review of existing literature on neurodegenerative disease mechanisms.
- Analysis of genetic variants contributing to disease pathogenesis.
- Examination of cellular and molecular pathways of protein aggregation.
Main Results:
- Identified shared mechanisms, including protein aggregation and inclusion body formation, across various neurodegenerative diseases.
- Highlighted that earlier steps in protein misfolding cascades may be more critical to pathogenesis than visible aggregates.
- Emphasized the role of genetic variants in understanding sporadic disease forms and developing disease models.
Conclusions:
- Protein aggregation is a central, unifying mechanism in neurodegenerative diseases.
- Targeting early steps in protein aggregation pathways offers a promising strategy for developing novel therapeutics.
- Further research into molecular mechanisms of cellular toxicity is crucial for advancing treatment approaches.
Related Concept Videos
03:03Amyloid Fibrils
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, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
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, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:13The Proteasome
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 (ubiquitin...
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 (ubiquitin...
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...
01:23Alzheimer 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...
01:24Parkinson 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...